Posts published in “Nutrition”

Is Calorie Restriction One of the Most Effective Anti-Ageing Methods?

By Agata Rzeszótko on November 1, 2025

Is Calorie Restriction One of the Most Effective Anti-Ageing Methods?

Highlights:

CR improves cardiometabolic health markers: Well-designed studies like CALERIE 2 demonstrate that even healthy, non-obese adults can experience meaningful improvements in cardiovascular risk factors, insulin sensitivity, inflammation, and body composition through moderate calorie restriction (10–25%).
A modest, nutrient-dense approach appears safe: For healthy adults, a moderate calorie reduction (10–25%) combined with a highly nutritious diet—inspired by traditional Okinawan eating patterns—offers low risk and potentially significant health benefits. The key is adequate nutrition: restriction without malnutrition.
Optimal BMI shifts with age: The traditional “healthy” BMI range (18.5–24.9) may not apply uniformly across the lifespan. For older adults (≥65 years), BMIs in the 24–30 range are associated with lower mortality, challenging the assumption that lower is always better.

What We Mean by “Calorie Restriction”

Common human-trial definition (aligned with National Institutes of Health guidelines): sustained energy intake below pre-intervention requirements with adequate nutrition. This initially causes weight loss, then metabolic adaptation and a stable lower body weight (Most & Redman, 2020).
Flanagan et al. (2020) define calorie restriction (CR) as reducing intake below energy requirements while maintaining optimal nutrition. Diets ranging from 10–30% CR have shown beneficial effects on ageing biomarkers and healthspan in animals and humans.
Alternative framing: intake well below ad libitum consumption—typically ≥10% in humans and ≥20% in animals (Bales & Kraus, 2013).

Protocols, baselines, and adherence tracking differ between studies, so “CR” means different things across papers.

Practical constraints matter. Severe CR ( ≥40%) can put patients at risk of adverse physical and psychological effects (Flanagan et al., 2020). Achieving adequate nutrition alongside CR can be challenging in practice without professional guidance.

Who Should Avoid CR?

Underweight individuals, those with a history of eating disorders, and patients with sensitive medical conditions (such as during active cancer therapy) should avoid calorie restriction. It is generally contraindicated due to risks of undernutrition and interference with treatment.

Who Can Benefit from CR?

Overweight and obese individuals clearly benefit from energy restriction. For this group, it may be the most effective intervention to improve cardiometabolic risk and extend healthspan, assuming no contraindications.
CR is a cornerstone of secondary prevention for cardiovascular disease, with well-established benefits for mortality, hospital readmission, functional capacity, and quality of life (Mueller & Kim, 2025).
Weight loss can produce remission of type 2 diabetes in a dose-dependent manner. A weight loss of ~15 kg through calorie restriction as part of an intensive management program can lead to remission in ~80% of patients with obesity and type 2 diabetes (Magkos et al., 2020).

But the key question here is: can a healthy person with normal body weight (BMI 18.5–24.99 kg/m²) benefit from calorie restriction in terms of longevity? Can CR extend healthspan (defined as “the part of a person’s life during which they are generally in good health”)?

BMI and Age: Rethinking Optimal Weight for Longevity

Before answering that question, we need to examine how we define normal body weight—and what problems might exist concerning that definition.

The WHO defines a healthy BMI range for adults as 18.5–24.9 kg/m², primarily based on a reduced mortality risk in younger populations. However, this standard may not apply uniformly across all age groups.

Research in older adults paints a more complex picture. Winter et al. (2014) found that for adults aged 65 and older, the relationship between BMI and all-cause mortality is U-shaped, with the lowest mortality risk occurring at BMIs between 24.0 and 30.9—considerably higher than the traditional “healthy” range (Winter et al., 2014).

This finding is what Sorkin (2014) describes as “the slaying of a beautiful hypothesis by an ugly fact.” The widely held belief that lower BMI always predicts better longevity has been challenged by robust epidemiological evidence showing that optimal BMI varies substantially with age.

Key insights from this editorial include:

The BMI-mortality relationship is U-shaped, not linear. Both low and high BMI are associated with increased mortality, with minimal risk typically occurring at BMIs of 26–29 in older adults—substantially higher than the conventional recommendation of around 21.
Optimal BMI shifts upward with age. In adults ≥65 years, BMIs in the overweight or mildly obese range are often associated with lower mortality compared to the “normal” BMI range, contradicting the hypothesis that lower BMI universally promotes longevity.
Earlier studies advocating low BMI often failed to adequately control for confounding factors such as smoking, preexisting illness, or reverse causation (where illness causes weight loss before death).
Modern large-scale studies using advanced statistical methods consistently show that minimum mortality BMI increases with age and does not differ significantly between genders.

Let’s remember that BMI is a population-level tool, not a precise measure of individual health. It doesn’t account for body composition, fitness, muscle mass, or underlying health conditions—all critical factors in assessing longevity risk.

Okinawa as a Case Study (Signal, Not Proof)

Okinawa’s reputation for healthy ageing is often linked to diet, with calorie restriction (CR) being highlighted as a possible key factor.

The most detailed look at CR in Okinawa drew on fifty years of nutrition, health, and population data. From the 1950s through the 1960s, surveys and health records suggested that Okinawan adults ate roughly 11% fewer calories per day (about 1,785 kcal) than the Harris-Benedict equation would predict for maintaining body weight. They appeared to be in a mild but sustained “energy deficit.” This pattern showed up in their bodies: lower weight, shorter stature, and a lean average BMI of 21 kg/m². Most people reach their peak weight in early adulthood and stay stable until old age. All of this fits the textbook picture of long-term calorie restriction as defined by NIH experts (Willcox & Willcox, 2014).

That said, calorie restriction remains one of the most debated factors in Okinawan longevity. The likely reason for our focus on CR is that in lab animals—yeast, worms, flies, and mice—it reliably delays disease and extends both average and maximum lifespan, provided nutrition remains adequate (Xie et al., 2021)

“Calorie restriction is currently one of the most feasible and effective anti-ageing methods” (Xie et al., 2021)

While we know this to be true in laboratory settings, we cannot confirm with complete certainty that the same effects occur in humans (Willcox & Willcox, 2014).

Worth noting: the traditional Okinawan diet in the 1960s was incredibly nutrient-dense and rich in polyphenols. Other important factors likely include regular, moderate physical activity, favourable genetics, and strong community support—all contributing to a low-stress, balanced lifestyle. Among the most underestimated factors may be the psychological and philosophical dimensions.

Ikigai (literally “a reason for being”) and nagomi (usually translated as “calm” or “harmony,” but referring to a broader philosophical concept of calmness and relaxation) are central to Japanese culture, yet their meaning can feel abstract and difficult to pursue within a Western lifestyle.

For a more scientific perspective on these ideas, I recommend “Flow: The Psychology of Optimal Experience” by Mihály Csíkszentmihályi. The book explores how the flow experience—finding joy and fulfilment through complete engagement in what you are doing—can lead to a richer, more meaningful life. It’s a must-read!

With so many factors at play, it’s impossible to pinpoint which one matters most for longevity. That said, I’ll revisit this topic in the future and share more about traditional Okinawan lifestyle practices as I find them truly fascinating.

Evidence from Other Human Studies

Research in healthy, non-obese adults offers some clues. Most et al. (2018) ran a landmark trial asking whether sustained CR could improve healthspan in people who were already “healthy” and not obese. Their hypothesis: CR would reduce cardiovascular disease risk and mortality while fundamentally enhancing the quality of ageing. The most striking finding? Even subjects without obesity or high CVD risk showed significant improvements in cardiometabolic markers with CR. Those benefits appeared to stem from improved body composition rather than enhanced aerobic fitness—CR reduced fat accumulation across adipose tissue depots without improving fitness measures. Whether these improvements can prevent or delay metabolic complications later in life for non-obese individuals remains an open question.

Much of this work has used the CALERIE 2 protocol, including the Most et al. (2018) study. Another major CALERIE 2 trial (Kraus et al., 2019) randomly assigned young and middle-aged adults (21–50 years) with healthy BMIs (22.0–27.9 kg/m²) to either 25% calorie restriction or an ad libitum control diet across three U.S. clinical centres. After two years, moderate calorie restriction significantly reduced multiple cardiometabolic risk factors in these young, non-obese participants—suggesting real potential for cardiovascular health benefits when healthy individuals practice moderate CR.

A comprehensive meta-analysis by Caristia et al. (2020) pulled together eight randomised controlled trials involving 704 participants (67.9% women, 10.5% lost to follow-up). The analysis found that CR prompted favourable changes across numerous health predictors of quality ageing: anthropometric measures, body composition, energy homeostasis, oxidative stress and inflammation markers, cardiovascular disease risk, insulin sensitivity, mood, well-being, and quality of life. But the authors noted important limitations. The relatively small number of studies and short follow-up periods prevented clear conclusions about CR’s relationship with chronic disease development. Current evidence also can’t identify an optimal “golden” calorie restriction level for improving long-term cardiometabolic health across all ages and weights, particularly after the restriction regime ends.

Bottom line: we need more well-designed controlled trials with larger sample sizes, normal-weight subjects, and longer follow-ups to better understand the mechanisms underlying CR’s health effects and to establish the safety of prolonged restriction regimens.

Mechanisms by Which Calorie Restriction Promotes Health and Longevity

The figure below illustrates the interconnected pathways through which calorie restriction (CR) influences ageing and disease prevention. CR triggers multiple molecular cascades:

Proposed hierarchical model: pathways by which calorie restriction may influence healthspan and longevity. Based on a figure from: Most J, Tosti V, Redman LM, Fontana L. Calorie restriction in humans: An update. Ageing Res Rev. 2017 Oct;39:36-45. doi: 10.1016/j.arr.2016.08.005. Epub 2016 Aug 17. PMID: 27544442; PMCID: PMC5315691.

CR activates heat shock proteins (HSF/HSP70) that maintain protein quality and reduce cellular senescence (def. loss of a cell’s power of division and growth). It also modulates key longevity pathways by decreasing insulin/IGF-1/mTOR signalling while increasing FOXO, SIRT, and AMPK activity, leading to enhanced autophagy, DNA repair, and reduced oxidative stress. Additionally, CR reduces chronic inflammation and lowers thyroid hormone T3 levels, which decreases metabolic rate and oxidative damage.

These molecular changes produce beneficial metabolic effects: improved insulin sensitivity with reduced compensatory hyperinsulinemia, decreased central adiposity, and favourable changes in sex hormones and IGFBP1 levels. The improved central adiposity further leads to better lipid profiles, lower blood pressure, and improved glucose control.

At the bottom of the diagram, these interconnected mechanisms converge to reduce the risk of three major age-related diseases: cancer, type 2 diabetes, and cardiovascular disease. Ultimately, by reducing cellular and molecular damage, enhancing stress resistance and repair mechanisms, and maintaining metabolic homeostasis, calorie restriction promotes increased healthspan and lifespan.

Take-Home Message

Calorie restriction (CR) shows promise as a method to improve healthspan in humans, but the evidence is still evolving, and context matters significantly.

While proclaiming CR as a universal anti-ageing prescription is premature, the available evidence suggests that modest (10-25%), well-nourished calorie restriction can be a plausible and effective strategy for many healthy adults to improve healthspan-related risk factors. More research with longer follow-ups is needed to confirm these benefits and determine optimal restriction levels across different ages and populations.

References

Bales, C. W., & Kraus, W. E. (2013). Caloric restriction: Implications for human cardiometabolic health. Journal of Cardiopulmonary Rehabilitation and Prevention, 33(4), 201–208. https://doi.org/10.1097/HCR.0b013e318295019e

Caristia, S., Vito, M., Sarro, A., Leone, A., Pecere, A., Zibetti, A., Filigheddu, N., Zeppegno, P., Prodam, F., Faggiano, F., & Marzullo, P. (2020). Is caloric restriction associated with better healthy aging outcomes? A systematic review and meta-analysis of randomized controlled trials. Nutrients, 12(8), 2290. https://doi.org/10.3390/nu12082290

Flanagan, E. W., Most, J., Mey, J. T., & Redman, L. M. (2020). Calorie restriction and aging in humans. Annual Review of Nutrition, 40, 105–133. https://doi.org/10.1146/annurev-nutr-122319-034601

Kraus, W. E., Bhapkar, M., Huffman, K. M., Pieper, C. F., Das, S. K., Redman, L. M., Villareal, D. T., Rochon, J., Roberts, S. B., Ravussin, E., Holloszy, J. O., & Fontana, L. (2019). 2 years of calorie restriction and cardiometabolic risk (CALERIE): Exploratory outcomes of a multicentre, phase 2, randomised controlled trial. The Lancet Diabetes & Endocrinology, 7(9), 673–683. https://doi.org/10.1016/S2213-8587(19)30151-2

Magkos, F., Hjorth, M. F., & Astrup, A. (2020). Diet and exercise in the prevention and treatment of type 2 diabetes mellitus. Nature Reviews Endocrinology, 16(10), 545–555. https://doi.org/10.1038/s41574-020-0381-5

Most, J., & Redman, L. M. (2020). Impact of calorie restriction on energy metabolism in humans. Experimental Gerontology, 133, 110875. https://doi.org/10.1016/j.exger.2020.110875

Most, J., Gilmore, L. A., Smith, S. R., Han, H., Ravussin, E., & Redman, L. M. (2018). Significant improvement in cardiometabolic health in healthy nonobese individuals during caloric restriction-induced weight loss and weight loss maintenance. American Journal of Physiology-Endocrinology and Metabolism, 314(4), E396–E405. https://doi.org/10.1152/ajpendo.00261.2017

Most, J., Tosti, V., Redman, L. M., & Fontana, L. (2017). Calorie restriction in humans: An update. Ageing Research Reviews, 39, 36–45. https://doi.org/10.1016/j.arr.2016.08.005

Mueller, A. S., & Kim, S. M. (2025). Cardiac rehabilitation in the modern era: Evidence, equity, and evolving delivery models across the cardiovascular spectrum. Journal of Clinical Medicine, 14(15), 5573. https://doi.org/10.3390/jcm14155573

Sorkin, J. D. (2014). BMI, age, and mortality: The slaying of a beautiful hypothesis by an ugly fact. The American Journal of Clinical Nutrition, 99(4), 759–760. https://doi.org/10.3945/ajcn.113.079343

Willcox, B. J., & Willcox, D. C. (2014). Caloric restriction, caloric restriction mimetics, and healthy aging in Okinawa: Controversies and clinical implications. Current Opinion in Clinical Nutrition & Metabolic Care, 17(1), 51–58. https://doi.org/10.1097/MCO.0000000000000019

Willcox, Donald & Willcox, Bradley & Todoriki, Hidemi & Suzuki, Makoto. (2009). The Okinawan Diet: Health Implications of a Low-Calorie, Nutrient-Dense, Antioxidant-Rich Dietary Pattern Low in Glycemic Load. Journal of the American College of Nutrition. 28 Suppl. 500S-516S. 10.1080/07315724.2009.10718117.

Winter, J. E., MacInnis, R. J., Wattanapenpaiboon, N., & Nowson, C. A. (2014). BMI and all-cause mortality in older adults: A meta-analysis. The American Journal of Clinical Nutrition, 99(4), 875–890. https://doi.org/10.3945/ajcn.113.068122

Xie, S.-H., Li, H., Jiang, J.-J., Quan, Y., & Zhang, H.-Y. (2021). Multi-omics interpretation of anti-aging mechanisms for ω-3 fatty acids. Genes, 12(11), 1691. https://doi.org/10.3390/genes12111691

Is Vitamin D The Greatest Longevity Vitamin?

By Agata Rzeszótko on October 1, 2025

Is Vitamin D The Greatest Longevity Vitamin?

Understanding Vitamin D

Vitamin D comes from two main sources:

Food sources – fatty fish, egg yolks, cheese, and mushrooms (particularly those exposed to UV light)

Vitamin D exists in multiple forms: D2 (ergocalciferol) found in mushrooms and yeast, and D3 (cholecalciferol), which is the primary form in humans. In countries where vitamin D-rich foods aren’t commonly consumed, fortified products like milk, butter, and cereals help address potential deficiencies (Magagnoli et al., 2025).

Selection of Japanese mushrooms at the Tokyo supermarket

Skin production – synthesis of vitamin D when exposed to sunlight

Research indicates that 80-90% of our vitamin D requirements are naturally met through skin synthesis. A 20-minute whole-body exposure to summer sunlight can produce approximately 250 μg of vitamin D3, achieving recommended serum levels of 25-hydroxyvitamin D (>30 ng/mL). The effectiveness of this synthesis varies based on exposure duration, season, and geographical latitude.

While vitamin D is best known for its role in calcium metabolism and bone health, its receptor (VDR) has been identified throughout the human body, including the skin, brain, immune cells, and pancreas. This widespread presence explains vitamin D’s beneficial effects on cardiovascular health, diabetes management, cancer prevention, mental health, cognitive function, multiple sclerosis, and fall prevention in elderly populations.

Today’s limited sun exposure due to clothing, indoor living, and varied climate conditions has made vitamin D deficiency a common issue, often requiring supplementation (Janoušek et al., 2022).

Testing and Supplementation

Vitamin D metabolism involves multiple steps before becoming biologically active. When vitamin D3 enters the bloodstream (whether from skin production or diet), it’s first processed in the liver to form calcidiol (25(OH)D3), then converted in the kidneys to the active form calcitriol (1,25(OH)2D3). Maintaining optimal liver stores of 25D3 is essential for proper vitamin D utilization (Kallioğlu, 2024).

Vitamin D deficiency represents a significant global health concern. Approximately 10% of Europeans have severe deficiency (less than 12 ng/mL), while deficiency rates (less than 20 ng/mL) reach around 20% in Northern Europe, 30-60% in other European regions, and as high as 80% in the Middle East.

Supplementation recommendations vary by organization and individual factors. The National Institutes of Health recommends 400-800 IU/day depending on age, with upper limits ranging from 1000-4000 IU/day. The Endocrine Society suggests higher upper limits (10,000 IU/day) than the Institute of Medicine (4000 IU/day). For individuals with normal levels, a standard dose of 1000 IU daily typically raises blood levels by 10 ng/ml over 3-4 months, though individual responses vary based on age, weight, skin color, and health conditions.

Natural vitamin D synthesis through sunlight exposure follows predictable patterns:

UVB exposure occurs primarily between 10:00-16:00, peaking at 12:30 pm
Active D3 synthesis happens from early March through late October in temperate regions
UVB radiation is minimal or absent during the winter months (November-February)
Skin type significantly affects production time – lighter skin (type I) requires about 5 minutes for 1000 IU, while darker skin (type VI) needs approximately 25 minutes
Latitude matters – for every degree away from the equator, D3 production decreases by 105 IU in summer and 237 IU in spring

In addition to general advice, it’s important to:

Get blood tests to check your actual vitamin D status
Adjust supplementation based on your specific levels
Remember that a vitamin D overdose, while rare, can be toxic

Sun Exposure and Alternatives

In my opinion, it’s better to protect skin from cancer and premature ageing by avoiding unprotected sun exposure (without SPF, sunglasses, hat, appropriate clothing) and instead relying on vitamin D supplementation.

Balancing sun exposure is important:

Some sunlight is essential for our circadian rhythm and sleep quality
From a longevity perspective, protecting our skin with sunscreen and sunglasses is recommended

Does SPF block vitamin D production? This remains controversial!

According to recent research, “The existing evidence supports that sunscreen can impair vitamin D3 synthesis, and as a result decrease serum 25(OH)D levels” (Gatta & Capelli, 2025). However, many studies note that sunscreen would need to be applied as a thick layer and regularly reapplied to fully block vitamin D production.

My recommendation: prioritise skin protection with SPF and other measures, then supplement vitamin D and incorporate more vitamin D3-rich foods to maintain healthy skin for years to come.

Effective Supplementation

Research shows that consistent, smaller daily doses of vitamin D are more effective than large weekly doses.

A clinical trial comparing equivalent doses of vitamin D3 (600 IU/day, 4200 IU/week, and 18,000 IU/month) in nursing home residents found daily administration most effective, while monthly dosing was least effective. After four months of treatment, 35% of those receiving monthly doses still had insufficient levels. Interestingly, calcium supplementation provided no additional benefit (Chel et al., 2007).

My advice: develop a consistent habit of taking vitamin D with breakfast daily. Separate calcium supplements aren’t necessary for vitamin D absorption.

Vitamin D and Longevity

Recent research demonstrates vitamin D’s potential impact on longevity and healthy ageing. The DO-HEALTH trial, examining 777 participants, found that vitamin D (2,000 IU daily), omega-3 (1g daily), and regular exercise showed additive benefits in slowing biological ageing markers. Over three years, these interventions demonstrated measurable protective effects on DNA methylation age markers (Bischoff-Ferrari et al., 2025).

Vitamin D has also gained attention as a neuroprotective agent. Low serum levels (<20 ng/mL) are associated with a 2.3-fold increased Alzheimer’s disease risk, while supplementation appears to slow cognitive decline in those with mild cognitive impairment (Li Y et al., 2025).

Further research indicates distinct roles for vitamin D in biological ageing processes, highlighting the importance of maintaining adequate levels for cognitive and physical health in older adults. Even among those with normal vitamin D levels, preserving cognitive function significantly slows biological ageing (Li M et al., 2025).

Vitamin D deficiency has been identified as a risk factor for decreased mobility in older individuals. Monitoring levels should be prioritised across clinical settings to minimise complications associated with deficiency, particularly regarding mobility (Luiz et al., 2025).

Studies examining exceptional longevity have found associations between vitamin D levels and cardiovascular health. Lower 25(OH)D levels are linked to increased risk of cardiovascular disease, hypertension, atherosclerosis, atrial fibrillation, and heart failure. Conversely, higher concentrations predict lower long-term mortality and cardiovascular disease incidence (Pareja-Galeano et al., 2015).

Recent research has also revealed vitamin D’s role in mitochondrial function. The vitamin D receptor (VDR) interacts with mitochondrial DNA, suggesting vitamin D’s involvement in cellular energy production and ageing processes (Gezen-Ak et al., 2023).

Take-home message

Vitamin D is essential for bone health and numerous body functions. While our bodies produce it naturally through sun exposure, modern lifestyles often lead to a deficiency. For optimal health, consider these key points:

Get your vitamin D levels tested to determine your personal needs
Daily supplementation (typically 1000-2000 IU) is more effective than weekly or monthly doses
Protect your skin with SPF and rely on supplements rather than unprotected sun exposure
Adequate vitamin D levels contribute to longevity, cognitive health, and reduced cardiovascular disease risk

References:

Bischoff-Ferrari, H., et al. (2025). Individual and additive effects of vitamin D, omega-3 and exercise on DNA methylation clocks of biological aging in older adults from the DO-HEALTH trial. Front. Aging, 12:1581612.

Chel, V., et al. (2007). Efficacy of different doses and time intervals of oral vitamin D supplementation with or without calcium in elderly nursing home residents. J Clin Endocrinol Metab, 92(7):2604-2609.

Gatta, L., & Capelli, G. (2025). Sunscreen and 25-Hydroxyvitamin D Levels: Friends or Foes? A Systematic Review and Meta-Analysis. Journal of Dermatology, 44(2):109-121. doi: 10.1016/j.eprac.2025.03.014

Gezen-Ak, D., et al. (2023). Vitamin D receptor regulates transcription of mitochondrial DNA and directly interacts with mitochondrial DNA and TFAM. J Nutr Biochem, 116:109322. doi: 10.1016/j.jnutbio.2023.109322

Kallioğlu, T. (2024). UV index‑based model for predicting synthesis of (pre‑)vitamin D3 in the mediterranean basin. Int J Biometeorol, 68(5):765-778.

Li, M., et al. (2025). Association of serum 25(OH)D3 and cognitive levels with biological aging in the elderly: a cross-sectional study. Front Nutr, 12:1581610. doi: 10.3389/fnut.2025.1581610

Li, Y., et al. (2025). The relationship between vitamin D levels and Alzheimer’s disease risk: insights from a centenarian study of Chinese women. Front Nutr, 12:1628732. doi: 10.3389/fnut.2025.1628732

Luiz, L.C., et al. (2025). Is serum 25-hydroxyvitamin D deficiency a risk factor for the incidence of slow gait speed in older individuals? Evidence from the English longitudinal study of ageing. Age and Ageing, 54(2):239-246.

Pareja-Galeano, H., et al. (2015). Vitamin D, precocious acute myocardial infarction, and exceptional longevity. Int J Cardiol, 199:405-6. doi: 10.1016/j.ijcard.2015.07.082

Can Omega-3 Fatty Acids Make You Live Longer?

By Agata Rzeszótko on September 1, 2025

Can Omega-3 Fatty Acids Make You Live Longer?

Understanding Fatty Acids

Before exploring our main topic, let’s begin with some fundamental knowledge about fatty acids.

Fatty acids can be classified into four basic groups based on their carbon chain length:

short-chain fatty acids (SCFAs), containing one to six carbon atoms (C1–6), form through carbohydrate fermentation by gut microbiota in mammalian digestive tracts
medium-chain fatty acids (MCFAs), containing seven to 12 carbon atoms (C7–12)
long-chain fatty acids (LCFAs), containing 14 to 18 carbon atoms (C14–18), which make up most dietary fatty acids
very long-chain fatty acids (VLCFAs), containing more than 20 carbon atoms (C > 20)

Fatty acids can also be categorised into saturated and unsaturated subgroups. The unsaturated category includes monounsaturated fatty acids (MUFAs), such as omega-9 fatty acids, and polyunsaturated fatty acids (PUFAs) (Cholewski et al., 2018).

Within the PUFA category, we find omega-6 and omega-3 fatty acids, which are the focus of this article.

Omega-3 fatty acids, a type of PUFA, are considered essential because human cells cannot produce them independently (Champigny et al., 2018). While some researchers consider all PUFAs essential, particularly highlighting linoleic acid (LA, an omega-6) and alpha-linolenic acid (ALA, an omega-3) as “parent essential fatty acids,” others focus on arachidonic (AA, an omega-6) and linoleic acids due to their role in growth and skin health. Mammalian research identifies 23 essential acids, while aquatic research focuses on just two omega-3s: EPA and DHA (Cholewski et al., 2018).

For our discussion of longevity, we’ll focus on three key omega-3 fatty acids: linolenic acid (ALA), eicosapentaenoic acid (EPA), and docosahexaenoic acid (DHA) (Xie et al., 2021).

Disclaimer: This graph is a simplified representation of the most relevant fatty acids mentioned in this article, that doesn’t show all existing fatty acids. It was created to clarify what omega-3 acids are, particularly EPA and DHA, in relation to omega-6 acids.

While the body cannot create omega-3 fatty acids from scratch, it can convert ALA (an 18-carbon fatty acid) into EPA (20 carbons) and subsequently into DHA (22 carbons) through enzymatic processes – but more on this process shortly (Xie et al., 2021).

ALA primarily comes from plant sources, especially seeds, nuts, and certain vegetable oils. Rich sources include flaxseed, chia seeds, walnuts and canola.

While safflower, sunflower, corn, and soybean oils contain high amounts of linoleic acid (LA, an omega-6), flaxseed oil is particularly rich in ALA (49.2 g/100 g).

For EPA and DHA, the best sources are fish oils, particularly from salmon, sardines, and herring (Shahidi & Ambigaipalan 2018).

An important nuance often overlooked is that nutritional choices aren’t black and white. While salmon is rich in EPA and DHA and eggs contain more saturated fats, this doesn’t mean we should exclusively eat salmon and completely avoid eggs. Eggs also contain omega-3 fatty acids, just in smaller quantities than salmon. It’s worth remembering that we consume whole foods, not isolated nutrients.

Salmon sashimi and tuna roll – an example of a dish rich in EPA and DHA.

Why Omega-3 Fatty Acid Supplementation Is Important

Two key challenges affect omega-3 levels in the body: omega-6 fatty acids compete with omega-3s for the same enzymes, and Western diets contain an excess of omega-6s.

The human body’s ability to convert ALA into EPA and DHA is remarkably inefficient. According to Shahidi & Ambigaipalan, only 0.2% of ALA converts to EPA, and a mere 0.05% converts to DHA.

Most people don’t get enough EPA and DHA through diet alone. This deficiency, combined with high omega-6 consumption, creates an unfavourable ratio of omega-6 to omega-3 fatty acids.

Understanding Ageing

Ageing is a complex biological process characterized by multiple interconnected mechanisms that contribute to the gradual decline of cellular and organismal function over time. Scientists have developed various frameworks to understand these mechanisms, with one prominent model being the Seven Pillars of Aging. This comprehensive framework breaks down the ageing process into distinct but interrelated biological components: inflammation (chronic low-grade inflammation that increases with age), metabolism (changes in how cells process energy and nutrients), epigenetics (alterations in gene expression patterns without DNA sequence changes), adaptation to stress (declining ability to respond to environmental challenges), stem cells and regeneration (reduced capacity for tissue repair and maintenance), macromolecular damage (accumulation of damaged proteins, lipids, and DNA), and proteostasis (declining ability to maintain proper protein folding and function) (Doyle et al., 2018).

Research on Omega-3 and Aging Mechanisms

Let’s explore in detail how omega-3 fatty acids interact with and influence the fundamental pillars of ageing, according to recent scientific research:

Inflammation
Omega-3 fatty acids, particularly EPA and DHA, act as activators for anti-inflammatory transcription factors. They compete with AA (arachidonic acid, sometimes encoded as ARA, omega-6 acid) to bind to substrates in enzymatic pathways, inhibiting the conversion of AA into pro-inflammatory molecules (Qiu et al., 2024).
Metabolism
Omega-3 fatty acids play a crucial role in metabolic regulation by influencing gut microbiota composition and function. They enhance fatty acid metabolism and improve nutrient absorption through multiple pathways in the digestive system (Qiu et al., 2024). So we could say that the impact of omega-3 and omega-6 fatty acids on ageing is partially mediated by the gut microbiome, including Actinobacteria, Bifidobacteria, and Streptococcus (Xie et al., 2021).
Epigenetics
Through complex mechanisms, omega-3 fatty acids influence DNA methylation patterns and modulate the expression of genes associated with longevity. This epigenetic regulation can have long-lasting effects on cellular function (Xie et al., 2021).
Adaptation to stress
These essential fatty acids enhance cellular resilience by activating the Nrf2 pathway and upregulating protective enzymes like HO-1. This provides a crucial defence against oxidative damage and environmental stressors (Qiu et al., 2024).
Stem cells and regeneration
Research has demonstrated that omega-3 fatty acids support nervous system development and maintenance, potentially influencing stem cell function and tissue regeneration capabilities (Xie et al., 2021).
Macromolecular damage
While studies show mixed results, a mini meta-analysis suggests that omega-3 fatty acids may have a role in telomere maintenance (Ali et al., 2022). The decrease in the omega-6:omega-3 ratio has been associated with longer telomere length, potentially due to reduced inflammatory processes and oxidative stress (da Silva et al., 2022).
While these studies suggest that omega-3 fatty acids may contribute to cellular longevity by helping maintain telomere length, this relationship remains under investigation and shouldn’t be considered definitively proven (Ali et al., 2022).
Proteostasis
Omega-3 fatty acids significantly impact cellular membrane properties and signalling pathways, contributing to proper protein folding and cellular homeostasis maintenance (Qiu et al., 2024).

Recommended Intake

To achieve beneficial effects, research indicates that adults should consume 250-500mg of combined EPA and DHA daily (Wu et al., 2024). This dosage supports healthy ageing across multiple physiological systems. Note that the FDA recommends limiting combined EPA and DHA intake from dietary supplements to 5g per day (Izadi et al., 2024).

Take-Home Message

Research demonstrates that omega-3 fatty acids may slow ageing through multiple pathways—improving brain function and structure, reducing inflammation, modulating immune responses, and enhancing mitochondrial function (Wu et al., 2024).

The EPA/AA ratio is particularly significant, as higher ratios correlate with lower all-cause mortality (Qiu et al., 2024).

For optimal results, focus on two key ratios:

Lower the omega-6 to omega-3 ratio in your diet.
Increase the omega-3 to total fatty acids ratio in your blood (aim for an Omega-3 Index above 8%) (Alsmari et al., 2023).

Before beginning supplementation, consider getting a blood panel analysis to measure your fatty acid and omega-3/omega-6 ratios. This will make it easier to adjust your omega-3 supplementation dosage, leading to more effective intervention.

Select high-quality fish oil supplements to avoid heavy metal contamination.

References

Ali, S. R., Amer, S. A., Abd-El Hameed, M. A., Hamza, M. A., & Hassan, M. A. (2022). The association between omega-3 supplementation and telomere length and telomerase activity: A mini meta-analysis. Lipids in Health and Disease, 21(1), 1-10. doi:10.1186/s12944-022-01662-6

Alsmari, W., Algethami, M. R., Felemban, E. M., Aldahlawi, A. M., & Algethami, S. R. (2023). The Role of Omega-3 Fatty Acids in Human Health: A Review. Current Nutrition & Food Science, 19(4), 460-472. doi:10.2174/1573401318666220719121310

Champigny, C. M., McNamara, R. K., & Stark, K. D. (2018). Omega-3 fatty acid deficiency throughout the lifespan: An overview with emphasis on the brain. Nutrients, 10(8), 1046. doi:10.3390/nu10081046

Cholewski, M., Tomczykowa, M., & Tomczyk, M. (2018). A comprehensive review of chemistry, sources and bioavailability of omega-3 fatty acids. Nutrients, 10(11), 1662. doi:10.3390/nu10111662

da Silva, G. C., Lyra e Silva, N. M., Sabia, A. C., & de Miranda Netto, M. V. (2022). Dietary factors and telomere length: A systematic review. European Journal of Clinical Nutrition, 76(4), 1-11. doi:10.1038/s41430-021-00996-1

Doyle, K. E., Brown, J. L., & Rasheed, A. (2018). Identifying core pillars of aging: A review of biological mechanisms. Aging Cell, 17(4), e12814. doi:10.1111/acel.12814

Izadi, M., Khorshidi, M., Khodadadi, S., & Mohammadi, H. (2024). Omega-3 fatty acids and human health: An updated systematic review. Journal of Functional Foods, 81, 105575. doi:10.1016/j.jff.2023.105575

Qiu, X., Krogh, V., Ricceri, F., & Bosetti, C. (2024). Omega-3 fatty acids and healthy aging: A systematic review. Nutrients, 16(1), 156. doi:10.3390/nu16010156

Shahidi, F., & Ambigaipalan, P. (2018). Omega-3 polyunsaturated fatty acids and their health benefits. Annual Review of Food Science and Technology, 9, 345-381. doi:10.1146/annurev-food-111317-095850

Wu, J., Wilson, K. M., Stampfer, M. J., & Willett, W. C. (2024). Omega-3 fatty acids and mortality risk: A systematic review and meta-analysis. BMJ Nutrition, Prevention & Health, 7(1), e000614. doi:10.1136/bmjnph-2023-000614

Xie, D., Gong, M., Wei, W., & Jin, J. (2021). Understanding the role of omega-3 fatty acids in aging: A review of mechanisms related to inflammation and gut microbiota. Nutrients, 13(11), 4079. doi:10.3390/nu13114079

Is the Mediterranean Diet an Ultimate Longevity Protocol?

By Agata Rzeszótko on August 1, 2025

Is the Mediterranean Diet an Ultimate Longevity Protocol?

The Mediterranean Diet (MedDiet) is one of the world’s most important and well-researched eating patterns. It’s more than just a healthy way of eating – it’s so special that in 2010, UNESCO named it an important part of humanity’s intangible cultural heritage. This recognition shows that it’s not just a collection of healthy foods but a cultural archetype encompassing food selection, processing, and distribution methods (Dominguez, 2021).

What is the Mediterranean Diet?

The Mediterranean Diet combines health and pleasure. Fresh vegetables and fruits are at its heart, complemented by wholesome grains and protein-rich legumes. The star of the show is extra virgin olive oil, lending its golden touch to both cooking and seasoning.

This diet celebrates the bounty of the sea with regular servings of fish and seafood while treating meat as an occasional treat rather than a daily necessity. Dairy appears in modest portions, mainly as yoghurt and carefully selected cheeses. Nature’s candy – fresh fruit – takes centre stage for dessert, making sugary treats a rare indulgence.

But the Mediterranean lifestyle extends beyond the plate. It’s about savouring each moment: cooking with aromatic herbs and spices, sharing meals with loved ones, and embracing the rhythm of life through daily physical activity. Even rest is elevated to an art form, with the traditional siesta offering a peaceful midday pause.

This approach to eating and living emphasizes a deep connection with nature, favouring locally sourced, minimally processed foods. Wine, when consumed, is treated not as a mere beverage but as part of the meal’s social fabric, enjoyed in moderation and always alongside food. (Dominguez, 2021).

In academic settings, baseline adherence to the Mediterranean diet can be measured by the MEDAS (Mediterranean Diet Adherence Screener), which is a 14-point scoring system. This screener includes specific criteria for scoring points based on various dietary habits.

This particular screener comes from the publication of Schroder et al., 2011.

MEDAS (Mediterranean Diet Adherence Screener)	Criteria for 1 point
Do you use olive oil as the principal source of fat for cooking?	Yes
How much olive oil do you consume per day (including that used in frying, salads, meals eaten away from home, etc.)?	≥4 tablespoons
How many servings of vegetables do you consume per day? Count garnish and side servings as 1/2 point; a full serving is 200 g.	≥2
How many pieces of fruit (including fresh-squeezed juice) do you consume per day?	≥3
How many servings of red meat, hamburger, or sausages do you consume per day? A full serving is 100–150 g.	<1
How many servings (12 g) of butter, margarine, or cream do you consume per day?	<1
How many carbonated and/or sugar-sweetened beverages do you consume per day?	<1
Do you drink wine? How much do you consume per week?	≥7 cups
How many servings (150 g) of pulses do you consume per week?	≥3
How many servings of fish/seafood do you consume per week? (100–150 g of fish, 4–5 pieces or 200 g of seafood)	≥3
How many times do you consume commercial (not homemade) pastry such as cookies or cake per week?	<2
How many times do you consume nuts per week? (1 serving = 30 g)	≥3
Do you prefer to eat chicken, turkey or rabbit instead of beef, pork, hamburgers, or sausages?	Yes
How many times per week do you consume boiled vegetables, pasta, rice, or other dishes with a sauce of tomato, garlic, onion, or leeks sauted in olive oil (so called “soffrrito”)?	≥2

MEDAS scores range from 0-14 points total. The scores indicate different levels of Mediterranean Diet adherence: scores of 5 or less show low adherence, scores between 6-9 show moderate adherence, and scores of 10 or higher show strong adherence (García-Conesa 2020).

Tomato soup (Italian: **Tuscan Pappa al Pomodoro)**

Mechanisms Behind the Benefits

One key mechanism explaining the MedDiet’s benefits involves the gut microbiota, which has emerged as a crucial player in the diet-health relationship through metabolites derived from microbial fermentation of nutrients, particularly short-chain fatty acids (Dominguez, 2021).

Research shows that looking at specific nutrients helps us understand healthy diets.

Dark-colored vegetables and fruits contain powerful anti-inflammatory and antioxidant compounds. These compounds appear in many different diets and may help explain why certain foods promote better health as we age (Hsiao & Chen 2022).

Polyphenols play a significant role in the diet’s effectiveness. In a Mediterranean cohort from Catania, Italy, the mean polyphenol intake was high (663.7 mg/d), with major sources including nuts, tea, coffee, fruits (especially cherries and citrus), vegetables (particularly artichokes and olives), chocolate, red wine, and pasta. Additionally, the PREDIMED trial demonstrated that a high intake of total polyphenols, especially stilbenes and lignans, was associated with reduced mortality risk. The distinguishing factor in PREDIMED participants was their consumption of polyphenols from olives and olive oil (Dominguez, 2021).

Impact on Mortality & Biological Ageing

Research consistently shows that increased adherence to the Mediterranean Diet pattern correlates with reduced total and cause-specific mortality. A comprehensive meta-analysis of 29 prospective observational studies, involving over 1.67 million participants, revealed a 10% reduction in all-cause mortality for every two-point increase in MedDiet adherence. The effect was even stronger among Mediterranean residents compared to non-Mediterranean populations (hazard ratios of 0.82 and 0.92, respectively) (Barber, 2023).

The diet’s impact on longevity is supported by biological evidence. Studies have shown that adherence to the Mediterranean Diet is associated with longer telomere length, suggesting it may also slow the biological ageing process (Barber, 2023).

Blue Zones: A Global Perspective on Longevity

The Blue Zones, areas with unusually high concentrations of centenarians, provide valuable insights into dietary patterns and longevity. These regions include Okinawa (Japan), Ikaria (Greece), parts of Sardinia (Italy), and the Nicoya Peninsula (Costa Rica) (Pes, 2022).

Dan Buettner, a National Geographic journalist, is credited with the concept of Blue Zones. In addition to the four locations mentioned above, a fifth one has been established: Loma Linda, California (United States of America) (Tan 2024).

These populations have been rigorously validated through death certificates and social security records. Interestingly, the dietary patterns across Blue Zones show remarkable diversity. Even within Mediterranean Blue Zones, there are significant deviations from the classical Mediterranean Diet (Pes, 2022).

Beyond Diet: A Complex Picture

The relationship between diet and longevity is more complex than often portrayed. In Sardinia’s Blue Zone, for example, potentially negative effects of a diet high in saturated fats and potato-derived starch were likely offset by the intense daily physical activity of their pastoral lifestyle. Additionally, genetic factors present in Blue Zone populations may have diminished the relative importance of diet in their exceptional longevity (Pes, 2022).

Recent research suggests that hybrid approaches might be beneficial. For instance, the Mediterranean-styled Japanese diet combines elements from both traditions, focusing on vegetables, beans, and fish while incorporating specific elements from both cultures. This fusion demonstrates how different healthy eating patterns can be adapted and combined (Santa, 2022).

Why the Mediterranean Diet Isn’t the Ultimate Protocol

While the Mediterranean Diet has proven benefits, calling it the “ultimate” longevity protocol would be an oversimplification. The evidence from Blue Zones shows that different dietary patterns can promote longevity when adapted to local contexts and individual needs. The success of any dietary pattern depends heavily on its interaction with lifestyle factors, genetics, and environmental conditions (Pes, 2022).

Furthermore, research on the transferability and effectiveness of the Mediterranean Diet in non-Mediterranean populations requires further investigation (Dominguez, 2021). What works in one population or region may not work equally well in another.

Conclusion: A Holistic Approach to Longevity

Medicine should aim not merely at life’s prolongation but at promoting old age while avoiding multimorbidity and disability as much as possible (Dominguez, 2021). The Mediterranean Diet can certainly be an excellent longevity protocol, but it’s just one component of a complex system that influences healthy ageing.

The key to understanding longevity lies in recognizing that dietary patterns are largely affected by culture, ethnicity, geographical locations, and cooking methods. As we continue to explore the fascinating field of longevity, we must consider diet as part of a broader lifestyle approach that includes physical activity, genetic factors, and various other elements that contribute to a long, healthy life.

Reference

Impact of Mediterranean Diet on Chronic Non-Communicable Diseases and Longevity (Dominguez et al., 2021) doi: 10.3390/nu13062028

A Short Screener Is Valid for Assessing Mediterranean Diet Adherence among Older Spanish Men and Women (Schroder et al., 2011) doi: 10.3945/jn.110.135566

Exploring the Validity of the 14-Item Mediterranean Diet Adherence Screener (MEDAS): A Cross-National Study in Seven European Countries around the Mediterranean Region (García-Conesa et al., 2020) doi: 10.3390/nu12102960

What constitutes healthy diet in healthy longevity (Hsiao & Chen 2022) doi: 10.1016/j.archger.2022.104761

The Effects of the Mediterranean Diet on Health and Gut Microbiota (Barber et al., 2023) doi: 10.3390/nu15092150

The Recommendation of the Mediterranean-styled Japanese Diet for Healthy Longevity (Santa et al., 2022) doi: 10.2174/0118715303280097240130072031

Diet and longevity in the Blue Zones: A set-and-forget issue? (Pes et al., 2022) doi: 10.1016/j.maturitas.2022.06.004

Navigating the Healthcare Conundrum: Leadership Perspective from a Premier Healthcare Organization in Loma Linda’s Blue Zone (Tan et al., 2024) doi: 10.2147/JHL.S452188