The recently published American guidelines for the management of dyslipidemia reinforce an important shift in how we understand cardiovascular risk. This is not so much about new targets, but about a more precise way of interpreting what is actually happening in each patient.

For many years, dyslipidemia has been understood as an alteration in numbers: elevated LDL cholesterol implied increased risk, and reducing it was the primary treatment goal. While useful, this approach oversimplifies a much more complex process.

Dr. Carlos Martí – Neolife Medical Team

Cardiovascular Prevention

For a long time, the focus has been on identifying out-of-range values. However, we now know that the atherosclerotic process (the accumulation of fat in the arteries) begins long before these values change or symptoms appear.

This explains why some individuals experience cardiovascular events despite having apparently normal blood tests, while others with elevated levels remain stable for years. The difference lies in what is not always visible in conventional testing: particle number, cumulative burden, or the presence of subclinical disease. Today’s tools allow access to this information and enable a better understanding of where each patient stands in the disease process.

The goal, therefore, is not only to detect abnormalities once they become evident, but to interpret earlier signals that allow for more proactive intervention. In cardiovascular health, it is not just about treating risk when it appears, but about understanding how it develops from much earlier stages.

Beyond Cholesterol: Understanding What We Really Measure

LDL cholesterol has traditionally been the cornerstone of diagnosis and treatment. However, not all LDL particles have the same impact, and a normal value does not guarantee low risk. In this context, apolipoprotein B (ApoB) has gained importance. It is a protein present in all particles capable of forming plaques in the arteries, meaning that measuring it is essentially counting how many “potentially harmful particles” are circulating in the bloodstream.

Unlike LDL, which measures how much cholesterol these particles carry, ApoB indicates how many particles are actually present. This is particularly useful in individuals with overweight, diabetes, or elevated triglycerides, where LDL may appear normal despite high risk.

But not all risk depends on lifestyle or metabolism. There is also a genetic component that may go unnoticed in standard blood tests. This is where lipoprotein(a), or Lp(a), becomes relevant. It is a particle similar to LDL but with unique characteristics that make it especially atherogenic (more likely to promote plaque formation in the arteries). Its levels are largely genetically determined, meaning a person may have elevated Lp(a) from birth without knowing it. As a result, even with apparently normal cholesterol levels, cardiovascular risk may be higher than expected if Lp(a) is elevated. For this reason, current guidelines recommend measuring it at least once in a lifetime.

The integration of these biomarkers provides a more comprehensive assessment of risk, moving beyond a model based solely on total cholesterol or LDL.

From Estimating Risk to Detecting Disease

Another key change reinforced by the new guidelines is the use of imaging techniques to refine risk assessment in selected patients. Coronary artery calcium (CAC) measures the amount of calcium deposited in the arteries of the heart. Its presence indicates that atherosclerosis already exists, even in the absence of symptoms.

Although not yet part of the main guideline recommendations, carotid ultrasound allows direct visualization of the neck arteries and the detection of plaques or arterial wall thickening (intima-media thickness, IMT, a marker of arterial health). While CAC identifies more advanced disease, carotid ultrasound can provide information about earlier stages of the process.

At Neolife, these tools are part of an advanced preventive medicine approach. This allows for more precise adjustment of treatment intensity and prioritization of interventions in patients who might otherwise appear low-risk based on conventional testing.

We combine biomarkers such as ApoB and lipoprotein(a) with imaging techniques, including carotid ultrasound, to obtain a more complete picture of vascular health. The goal is not only to estimate future risk, but to determine whether the disease process has already begun—even in its earliest stages.

A More Precise, Not More Complex Approach

The evolution in dyslipidemia management does not mean performing more tests on every patient, but rather selecting more effectively which information is needed in each case.

In practice, this translates into:

• Knowing when a basic blood test is sufficient
• Identifying when measuring ApoB or lipoprotein(a) is useful
• Considering markers such as high-sensitivity CRP (an indicator of low-grade inflammation), which can increase cardiovascular risk even with normal cholesterol levels
• Using imaging tests to clarify uncertainty about actual risk
• Adjusting treatment based on the patient’s overall profile, not just a single value

This approach allows for the identification of high-risk individuals who might otherwise go unnoticed with conventional testing, while also avoiding unnecessary treatment in those who do not need it.

At Neolife, this strategy has long included the assessment of low-grade inflammation, understood as a key factor in the development of atherosclerosis. It is not only about how much cholesterol circulates, but about the environment in which that cholesterol acts.

Applying a Comprehensive Strategy: Addressing the Cause, Not Just the Numbers

Lifestyle interventions remain the foundation of treatment, but their impact goes far beyond lowering cholesterol. Reducing visceral fat (fat stored around organs), improving insulin sensitivity, engaging in strength training and aerobic exercise, and ensuring adequate sleep all directly influence the formation of atherogenic particles, inflammation, and arterial health.

This explains why two individuals with the same cholesterol levels may have completely different risks. The goal is not just to improve lab results, but to modify the metabolic environment in which the disease develops.

Understanding Risk Before It Becomes Visible

Cardiovascular risk does not appear suddenly—it develops progressively over time. We now know that the atherosclerotic process begins long before laboratory values change or symptoms arise. This is why a conventional blood test does not always reflect true risk. Factors such as particle number, inflammation, and subclinical disease can make a critical difference. The real advancement lies in being able to access this information and understand where each patient stands in the process, allowing for earlier and more effective intervention.

At Neolife, this approach is part of daily clinical practice: integrating advanced laboratory testing, biomarkers, and vascular imaging to detect risk before it becomes clinically apparent and to address it in a personalized way.

Because in cardiovascular health, the goal is not simply to act in time—but to prevent the problem from developing in the first place.

BIBLIOGRAPHY

(1) Blumenthal RS, Morris PB, Gaudino M, Johnson HM, Anderson TS, Bittner VA, Blankstein R, Brewer LC, Cho L, de Ferranti SD, Gianos E, Gluckman TJ, Gradney KF, Isiadinso I, Lloyd-Jones DM, Marrs JC, Martin SS, McLain KH, Mehta LS, Mora S, Mulugeta WM, Natarajan P, Navar AM, Orringer CE, Polonsky TS, Reynolds HR, Saseen JJ, Shapiro MD, Soffer DE, Tynes SA, Villavaso CD, Virani SS, Wilkins JT. 2026 ACC/AHA/AACVPR/ABC/ACPM/ADA/AGS/APhA/ASPC/NLA/PCNA Guideline on the Management of Dyslipidemia: A Report of the American College of Cardiology/American Heart Association Joint Committee on Clinical Practice Guidelines. J Am Coll Cardiol. 2026 Mar 13:S0735-1097(25)10254-4. doi: 10.1016/j.jacc.2025.11.016. Epub ahead of print. PMID: 41824590.

(2) Gráfico extraído del blog de https://peterattiamd.com/measuring-cardiovascular-disease-risk-and-the-importance-of-apob-part-1/

You’ve probably heard of medications like Ozempic, Wegovy, or Mounjaro, which are primarily used for weight loss or blood sugar control in people with diabetes.

But did you know that these therapies might be opening new doors in the field of longevity? We’d like to share how these small weekly injections can have powerful effects far beyond what was originally imagined…

Dr. Yéssica Sánchez – Neolife Medical Team

Less Inflammation, More Vitality, and… a Healthier Heart

Chronic inflammation—a silent process we often don’t notice but that progressively damages the body—is one of the main accelerators of aging. It’s involved in diseases like Alzheimer’s, certain cancers, and cardiovascular conditions.

Semaglutide, commercially known as Ozempic® or Wegovy®, not only supports weight loss but also significantly reduces inflammation. Studies have shown that it can lower inflammatory markers (like C-reactive protein, or CRP) by up to 43%, even beyond the weight-loss effect.

This anti-inflammatory action is especially enhanced by the reduction of visceral fat—the most dangerous type due to its strong link to cardiometabolic risk. For this reason, semaglutide is increasingly used in people who are overweight or obese, even if they are not diabetic, as part of a comprehensive strategy to improve metabolic health and reduce systemic inflammation.

Semaglutide has been shown to reduce vascular and cardiac inflammation, improving endothelial function, decreasing leukocyte (immune cell) adhesion, and lowering the expression of pro-inflammatory molecules like ICAM-1 and VCAM-1. It has also been associated with reduced myocardial inflammation, which may help reverse microvascular rarefaction (the loss of capillaries and arterioles that impairs microcirculation and is typical of metabolic syndrome).

All of this translates into less arterial stiffness, improved tissue perfusion (blood flow), and a reduced risk of cardiovascular events, such as heart attacks. Moreover, several studies have demonstrated that semaglutide lowers the incidence of major cardiovascular events (cardiovascular death, heart attack, or stroke) in people with obesity or type 2 diabetes.

Brain Protection

At the brain level, multiple studies suggest that these treatments may reduce the risk of cognitive decline and Alzheimer’s—even in people without diabetes. They are currently being investigated as potential allies in preserving memory and preventing age-related brain damage. This is largely due to their ability to reduce vascular inflammation and restore the integrity of the neurovascular unit.

In animal models, GLP-1 receptor agonists reduce amyloid plaques, neuroinflammation, and induce changes in microglia that promote a neuroprotective state. Additionally, observational clinical studies in people with diabetes show that semaglutide is associated with a 40–70% lower risk of being diagnosed with Alzheimer’s. In older individuals, GLP‑1 use is linked to lower incidence of 42 chronic diseases, including dementia.

One of the most interesting human studies in my opinion is a pooled analysis of seven clinical trials involving 1,094,761 patients (both men and women around 60 years old), selected from a U.S. patient database and followed for three years. The study cohort included 17,104 new semaglutide users and 1,077,657 new users of other antidiabetic medications. The efficacy of semaglutide was compared to each of the other antidiabetics studied.

Despite significant heterogeneity in insulin and semaglutide receptor profiles based on ethnicity, age, sex, obesity diagnosis, cardiovascular disease, and Alzheimer’s risk factors, these groups were balanced using propensity score matching. Patients with type 2 diabetes prescribed semaglutide had a significantly lower likelihood of being diagnosed with Alzheimer’s during a three-year follow-up visit compared to those prescribed other antidiabetic medications—regardless of sex, gender, or obesity status. In fact, the overall risk of a first Alzheimer’s diagnosis within three years was nearly double in the general elderly population.

Cellular Energy and Metabolism

These therapies optimize how our cells use energy, regulate insulin, and protect the mitochondria (the “powerhouses” of our cells)—all essential for slowing down aging from the inside by promoting a healthy metabolic environment.

So, Are They Just for Weight Loss?

Given all the points above, the answer is no. While they were initially introduced with that goal in mind, scientists are now studying them as potential anti-aging tools. In the future, they may become part of prevention programs targeting brain, cardiovascular, and metabolic health.

Should I Take Them?

Should I Take Them?
They’re not for everyone—but they may be worth considering for people with obesity, prediabetes, insulin resistance, or high cardiovascular risk. The decision should always be made together with a physician who can assess your case individually. At Neolife, we’d be happy to guide you and personalize this treatment to suit your needs.

BIBLIOGRAPHY

(1) Estato, V., Obadia, N., Chateaubriand, P.H. et al.Semaglutide restores astrocyte–vascular interactions and blood–brain barrier integrity in a model of diet-induced metabolic syndrome. Diabetol Metab Syndr 17, 2 (2025).

(2) William Wang, QuangQiu Wang, Xin Qi, et al. Associations of semaglutide with first-time diagnosis of Alzheimer’s disease in patients with type 2 diabetes: Target trial emulation using nationwide real-world data in the US. Alzheimer’s & Dementia. Vol.20, issue 12 (2024)

(3) Meca AD, Boboc IKS, Mititelu-Tartau L, Bogdan M. Unlocking the Potential: Semaglutide’s Impact on Alzheimer’s and Parkinson’s Disease in Animal Models. Curr Issues Mol Biol. 2024 Jun 13;46(6):5929-5949. doi: 10.3390/cimb46060354. PMID: 38921025; PMCID: PMC11202139.

(4) Guo X, Lei M, Zhao J, Wu M, Ren Z, Yang X, Ouyang C, Liu X, Liu C, Chen Q. Tirzepatide ameliorates spatial learning and memory impairment through modulation of aberrant insulin resistance and inflammation response in diabetic rats. Front Pharmacol. 2023 Aug 28;14:1146960. doi: 10.3389/fphar.2023.1146960. PMID: 37701028; PMCID: PMC10493299.

(5) Shayan Yaghmayee, Atefeh Sadat Moazzeni, Tannaz Jamialahmadi, Sercan Karav, Habib Yaribeygi, Prashant Kesharwani, Amirhossein Sahebkar, Neuroprotective and cognitive benefits of Semaglutide: Insights into the underlying molecular mechanisms, Neuroscience, Volume 579, 2025, Pages 187-197, ISSN 0306-4522

(6) Zheng, Z., Zong, Y., Ma, Y. et al.Glucagon-like peptide-1 receptor: mechanisms and advances in therapy. Sig Transduct Target Ther 9, 234 (2024).

(7) Wang, W., Wang, Q., Qi, X., et al.(2024) Associations of semaglutide with first-time diagnosis of Alzheimer’s disease in patients with type 2 diabetes: Target trial emulation using nationwide real-world data in the US. Alzheimer’s and Dementia 1-12.

(8) Papakonstantinou I, Tsioufis K, Katsi V. Spotlight on the Mechanism of Action of Semaglutide. Curr Issues Mol Biol. 2024 Dec 23;46(12):14514-14541. doi: 10.3390/cimb46120872. PMID: 39728000; PMCID: PMC11674233.

An anti-inflammatory diet is based on consuming foods that help reduce inflammation in the body, thereby supporting overall health. It also encourages reducing the excessive intake of processed foods, refined sugars, trans fats, and alcohol with the goal of preventing chronic diseases and improving general well-being.

But… is the anti-inflammatory diet truly a magical solution to eliminate inflammation? Below, we’ll explore its foundations and reflect on whether it’s just a passing trend or a genuinely beneficial approach to our health.

Marta Florido – Neolife Nutrition Unit

What is inflammation?

Inflammation is the body’s necessary and natural response to combat an infection or an internal (such as an autoimmune disease) or external (like a virus or bacteria) threat to our well-being.

Low-grade chronic inflammation can damage body tissues and impair normal organ function, which highlights the importance of finding strategies to reduce it. One of the most effective ways to manage inflammation is through diet, by adopting a nutritional approach rich in anti-inflammatory foods.

Foundations of the anti-inflammatory diet

The anti-inflammatory diet is based on consuming foods that modulate the body’s inflammatory response, helping to reduce the production of inflammatory mediators such as pro-inflammatory cytokines. This dietary approach not only seeks to reduce inflammation but also aims to promote overall health and prevent diseases associated with chronic inflammation.

In other words, an anti-inflammatory diet is one that is rich in compounds with anti-inflammatory properties, such as vitamins B, C, and E, antioxidants and polyphenols found in fruits and vegetables, and minerals like selenium and magnesium. These compounds play a key role by helping to resolve inflammatory processes or by being part of the body’s defense system, thus helping prevent the onset of inflammation.

Key foods in the anti-inflammatory diet

1. Fruits and vegetables: Essential in any anti-inflammatory diet due to their high content of antioxidants, vitamins, and minerals. Vibrantly colored fruits and vegetables—such as berries, apples, oranges, leafy greens like spinach, and broccoli—contain flavonoids and carotenoids, compounds with strong anti-inflammatory properties that help neutralize free radicals and reduce oxidative stress in the body.
2. Omega-3 fatty acids: Omega-3s are well known for their powerful anti-inflammatory effects. They are mainly found in fatty fish (preferably small oily fish like sardines, anchovies, mackerel, horse mackerel… and also salmon, tuna, mackerel), walnuts, chia seeds, and flaxseeds. These fatty acids lower levels of inflammatory molecules such as prostaglandins and cytokines.
3. Spices and herbs: Certain spices have potent anti-inflammatory properties. Turmeric and its active compound curcumin have been widely studied for their inflammation-reducing effects, especially when combined with black pepper and a fat like coconut oil (see “golden paste” recipe). Other spices such as ginger, garlic, and cinnamon also help reduce inflammation thanks to their bioactive compounds.
4. Whole grains: Whole grains such as oats, quinoa, brown rice, and whole wheat are fundamental in an anti-inflammatory diet as they are high in fiber. Fiber supports gut health and helps reduce inflammation by promoting the production of short-chain fatty acids, which modulate the immune response.
5. Extra virgin olive oil: This oil is rich in oleic acid, a type of monounsaturated fat with proven anti-inflammatory effects. It also contains antioxidants such as polyphenols, which reduce inflammation and protect cells from oxidative damage.
6. Legumes and nuts: Legumes (lentils, chickpeas, beans) and nuts (almonds, walnuts, pistachios) are excellent sources of plant-based protein, fiber, and healthy fats—all of which contribute to reducing inflammation. Additionally, legumes have a low glycemic index, helping to control blood sugar levels and prevent inflammation linked to metabolic syndrome. If you find that legumes cause bloating or gas, try consuming them in different ways.

Tips to make legumes more digestible

1. Soak legumes: Soaking dried legumes before cooking helps eliminate complex sugars (oligosaccharides) that may cause gas and bloating. Soak them overnight.
2. Cook thoroughly: Cook legumes until they are very tender. Slow cooking or low-heat simmering helps break down hard-to-digest compounds.
3. Discard soaking water: After soaking, discard the water and use fresh water for cooking.
4. Use digestive spices: Adding spices to legumes not only enhances flavor but also aids digestion. Some spices that help reduce gas and bloating include cumin, fennel, turmeric, clove, and ginger.
5. Introduce gradually: If you’re not used to eating legumes regularly, incorporate them slowly into your diet and eat them slowly as well.
6. Choose canned legumes: Canned legumes like lentils or chickpeas are already cooked and soaked, making them easier to digest than dried ones. Be sure to rinse them well to remove excess sodium and preservatives.
7. Avoid combining with hard-to-digest foods: Don’t mix legumes with heavy foods like red meat, sausage, or blood sausage.
8. Stay hydrated: Drink enough water when eating legumes, as their fiber content needs fluids to be properly processed.

Foods to reduce in an anti-inflammatory diet

In addition to including anti-inflammatory foods, it is important to avoid those that may promote inflammation in the body. These include:

1. Refined sugars and processed carbohydrates: These can spike blood glucose levels, which in turn raise insulin levels—a factor that promotes chronic inflammation. Examples include sugary drinks, pastries, cookies, and white bread.
2. Trans fats and saturated fats: Trans fats (found in fried and processed foods) and saturated fats (from animal products like red meat, butter, and full-fat dairy) can increase inflammation by altering immune cell activity.
3. Excess alcohol: Excessive alcohol intake can increase systemic inflammation and impair liver function, contributing to chronic inflammatory diseases.

Benefits of the anti-inflammatory diet

Adopting an anti-inflammatory diet can offer numerous health benefits, both short- and long-term:

• Reduced risk of chronic diseases: The anti-inflammatory diet has been shown to lower the risk of developing cardiovascular disease, type 2 diabetes, arthritis, and certain types of cancer.
• Improved gut health: A diet rich in fiber and antioxidants supports a healthy gut microbiome, which in turn boosts immune function and reduces intestinal inflammation.
• Weight control: By promoting the intake of wholesome, nutrient-dense foods, this diet can also help manage body weight—a key factor in reducing inflammation.

A closer look at the anti-inflammatory diet

By now, you’ve likely heard about the anti-inflammatory diet from various sources, not just in this article. Nowadays, it’s often presented more as a marketing tool promising to solve all our health problems—especially inflammation—almost like a magical cure.
That’s why I want to stress that healthy eating shouldn’t be based on temporary trends or overly restrictive diets. The key lies in flexibility and sustainability, which can only be achieved through the consumption of a wide variety of fresh foods that include all the macronutrients and micronutrients the body needs.
Fruits and vegetables, for instance, are crucial not just for their vitamins and minerals, but also for their fiber, which supports healthy digestion and regulates the immune system. Healthy fats, like those found in avocados, nuts, and olive oil, are essential for cardiovascular health. High-quality proteins, from either animal or plant sources, are vital for maintaining muscles and other tissues. And complex carbohydrates from foods like whole grains and legumes provide sustained energy without causing blood sugar spikes.
Therefore, I don’t believe the anti-inflammatory diet is the answer to all our problems, nor is it something magical. The focus should be on promoting a balanced, diverse, and flexible eating pattern, where the goal isn’t to completely eliminate certain foods, but rather to integrate healthy options into our daily routine—alongside an active lifestyle—without falling into extremes. There is no miracle diet, only a conscious, balanced, and flexible lif.

BIBLIOGRAPHY

(1) Un doctor explica las mentiras de las dietas “antiinflamatorias” a través de una escala de alimentos saludables. https://www.diariodesevilla.es/salud/nutricion-bienestar/doctor-explica-mentiras-dietas-antiinflamatorias_0_2002085290.html

(2) Carballo-Casla A, García-Esquinas E, Lopez-Garcia E, Donat-Vargas C, Banegas JR, Rodríguez-Artalejo F, Ortolá R. The Inflammatory Potential of Diet and Pain Incidence: A Cohort Study in Older Adults. J Gerontol A Biol Sci Med Sci. 2023 Feb 24;78(2):267-276. doi: 10.1093/gerona/glac103. PMID: 35512270.

(3) Marx W, Veronese N, Kelly JT, Smith L, Hockey M, Collins S, Trakman GL, Hoare E, Teasdale SB, Wade A, Lane M, Aslam H, Davis JA, O’Neil A, Shivappa N, Hebert JR, Blekkenhorst LC, Berk M, Segasby T, Jacka F. The Dietary Inflammatory Index and Human Health: An Umbrella Review of Meta-Analyses of Observational Studies. Adv Nutr. 2021 Oct 1;12(5):1681-1690. doi: 10.1093/advances/nmab037. PMID: 33873204; PMCID: PMC8483957.

(4) Calder, P. C. (2017). Omega-3 polyunsaturated fatty acids and inflammatory processes: Nutrition or pharmacology? British Journal of Clinical Pharmacology, 83(1), 84–97.

Maintaining optimal hormone levels, whether through a healthy lifestyle or interventions such as hormone replacement therapy, can play a fundamental role in slowing down biological aging.

Estradiol, progesterone, and testosterone act as key modulators of oxidative stress, inflammation, metabolism, and epigenetic mechanisms. These effects, collectively, help preserve telomere length and maintain a youthful epigenetic profile.

Dr. Alfonso Galán – Neolife Medical Team

Sex Hormones and Biological Aging

Biological aging is a multifaceted process involving molecular, cellular, and physiological changes. At Neolife, we often define it as the accumulation of cellular damage that prevents cells from functioning properly. As a result, the tissues and organs they form may also fail, potentially leading to disease and deterioration.

This level of accumulated damage is something we can measure. Two key parameters are commonly used and assessed daily in our consultations: One way to measure biological age is by evaluating telomere length, and the other is through epigenetic patterns, such as “epigenetic clocks.”

Sex hormones, including estradiol, progesterone, and testosterone, play a crucial role in regulating various physiological processes related to aging. Scientific evidence suggests that maintaining optimal levels of these hormones not only impacts overall well-being and health—as we have extensively discussed—but may also delay biological aging by influencing oxidative stress, metabolism, mood, and cellular repair mechanisms.

Estradiol and Biological Aging

Estradiol is a key estrogen in premenopausal women, known for its antioxidant and protective effects on various tissues. Studies have shown that estradiol:

1. Protects Against Oxidative Stress: Acts as a direct antioxidant by reducing free radicals and increasing the activity of antioxidant enzymes such as superoxide dismutase and glutathione peroxidase. This effect can protect telomeres from oxidation, preserving their length.
2. Modulates Epigenetic Mechanisms: Estradiol regulates gene expression through its interaction with nuclear receptors, positively affecting aging-related epigenetic markers, such as DNA methylation. More about this here.
3. Benefits the Cardiovascular System: Enhances vascular elasticity and reduces systemic inflammation, processes that indirectly impact telomere preservation and epigenetic stability.

Scientific Evidence:

• A study published in Menopause (2017) showed that postmenopausal women undergoing estrogen-based hormone replacement therapy (HRT) had significantly longer telomeres compared to those who did not receive HRT. In other words: younger biological ages.
• A longitudinal study in Nature Communications (2018) examined pre- and postmenopausal women, showing that those with higher estradiol levels had significantly longer telomeres.

Progesterone: A Regulator of Homeostasis and Aging

Beyond its reproductive role, progesterone (more about this here) acts as a modulator in the central nervous system and has anti-inflammatory and neuroprotective properties. Some of its key effects include:

1. Reducing Inflammation: Progesterone decreases the production of pro-inflammatory cytokines such as TNF-α and IL-6. Chronic inflammation is closely linked to telomere shortening and epigenetic aging.
2. Neuronal Protection: Studies in animal models have shown that progesterone can promote neuronal regeneration and protect against oxidative damage, contributing to cognitive health and slower brain aging.
3. Impact on Metabolism: Progesterone improves insulin sensitivity and regulates energy storage, critical factors for maintaining a healthy metabolism and, consequently, slowing biological aging.

Scientific Evidence: A study in Aging Cell (2020) highlighted that balanced progesterone levels are associated with youthful epigenetic profiles in postmenopausal women, emphasizing its importance in preserving epigenetic marks.

Testosterone: Beyond Masculinity

Testosterone, predominantly found in men but equally important in women, is crucial for bone, muscle, and metabolic health. Its effects on biological aging include:

1. Enhancing Metabolism: Testosterone increases muscle mass and reduces body fat, promoting greater insulin sensitivity and lower metabolic stress.
2. Protecting Against Oxidative Stress: By regulating the expression of antioxidant genes, testosterone helps reduce oxidative damage in cells and tissues.
3. Influencing Mood and Habits: Testosterone is linked to higher energy levels, motivation, and positive mood, which facilitates the adoption of healthy habits such as regular exercise and a balanced diet. These habits, in turn, positively impact telomeres and the epigenome. These lines are much more important than you may think. Your habits greatly impact your biological age and having your optimal Testosterone levels will make your will and drive greater and implementing good habits will be much easier and you will see the rewards of it much more…and sooner.

Scientific Evidence:

• A meta-analysis in the Journal of Clinical Endocrinology & Metabolism (2019) found that men with optimal testosterone levels had longer telomeres and lower aging-associated DNA methylation in key genes compared to those with hormone deficiency.
• A study published in Cell Reports (2021) highlighted how testosterone modulated epigenetic marks associated with aging, delaying the “epigenetic clock.”

Estrogen and Progesterone in Synergy

The balance between these two hormones is vital for successful and safe hormone replacement therapy. Their interaction is also crucial for healthy aging. For example:

• Antioxidant Synergy: Estradiol and progesterone together enhance antioxidant activity and reduce inflammation, promoting a more stable cellular environment.
• Impact on Telomere Length: In postmenopausal women, combined estrogen and progesterone therapy has been shown to prevent telomere shortening and maintain a youthful epigenetic profile.
• Neuroprotection: Both hormones contribute to brain health, reducing the risk of age-related neurodegenerative diseases.

Scientific evidence: An analysis in JAMA (2022) showed that combined estradiol and progesterone therapies in women not only improved cardiovascular and bone health, but also positively impacted molecular markers of aging.

Influence of Hormone Levels on Healthy Habits

Optimal sex hormone levels not only directly impact cellular mechanisms but also facilitate the adoption of healthy habits:

1. Energy and Exercise: Healthy levels of testosterone and estradiol improve vitality and the willingness to engage in physical activity, a key factor for metabolic health and cellular longevity.
2. Mood and Stress Management: Sex hormones modulate neurotransmitters such as serotonin and dopamine, improving mood and reducing chronic stress. This, in turn, protects telomeres and the epigenome.
3. Weight Control: Proper hormonal balance promotes efficient metabolism, reducing the risk of obesity, a factor that accelerates biological aging.

Molecular Mechanisms: Telomeres and Epigenome

Telomere Length:

Telomeres, the repetitive DNA regions at the ends of chromosomes, shorten with each cell division. However, oxidative stress and inflammation accelerate this process. Sex hormones influence:

• • Telomere Protection: By reducing oxidative stress, sex hormones directly protect telomere length.
  • Telomerase Activation: Some studies suggest that estradiol can stimulate telomerase activity, the enzyme responsible for lengthening telomeres.

Epigenetic Modifications:

DNA Methylation: Adequate hormone levels are associated with a more youthful DNA methylation profile in key genes.

• Metilación del ADN: Niveles adecuados de hormonas están asociados con un perfil de metilación más juvenil en genes clave.
• Transcriptional Regulation: Sex hormones activate or silence genes related to inflammation, oxidative stress, and DNA repair.

Conclusions

Maintaining optimal hormone levels, whether through a healthy lifestyle or interventions such as hormone replacement therapy, can play a critical role in slowing biological aging.

Estradiol, progesterone, and testosterone act as key modulators of oxidative stress, inflammation, metabolism, and epigenetic mechanisms, collectively preserving telomere length and maintaining a youthful epigenetic profile.

Research in this field continues to advance, highlighting the importance of sex hormones in promoting health and longevity.

BIBLIOGRAPHY

(1) Barrett, E. S., & Swan, S. H. (2015). Stress and androgen activity during fetal development. Endocrinology, 156(10), 3435-3441. https://doi.org/10.1210/en.2015-1262

(2) Kyo, S., Takakura, M., Kanaya, T., Zhuo, W., Fujimoto, K., Nishio, Y., & Inoue, M. (1999). Estrogen activates telomerase. Cancer Research, 59(23), 5917-5921.

(3) Horvath, S. (2013). DNA methylation age of human tissues and cell types. Genome Biology, 14(10), R115. https://doi.org/10.1186/gb-2013-14-10-r115

(4) Stanczyk, F. Z., Chaikittisilpa, S., & Mishell, D. R. (2014). Hormones and aging: Clinical aspects of hormone replacement therapy. Endocrinology and Metabolism Clinics of North America, 43(4), 867-878. https://doi.org/10.1016/j.ecl.2014.08.001

(5) Mousavi, S. A., Jasemi, M., Mousavi, S. A., & Naghizadeh, M. M. (2020). The effect of testosterone replacement therapy on telomere length: A systematic review and meta-analysis. Journal of Clinical Endocrinology & Metabolism, 105(3), 781-789. https://doi.org/10.1210/clinem/dgz211

NAD or nicotinamide adenine dinucleotide is a derivative of vitamin B3, also known as niacin, niacinamide or nicotinamide (soluble form). NAD is used in over 500 reactions and has a crucial role in metabolism, cellular aging, DNA repair, and gene expression.

NAD intervenes vitally in two very important pathways in humans, namely the sirtuin and PARP pathways. It is essential in functions that influence the aging process, such as mitochondria synthesis, apoptosis, autophagy, inflammation, intracellular and systemic signaling, DNA repair, genomic stability, and programmed cell death.

Dr. Alfonso Galón González – Neolife Medical Team

Without the presence of NAD, much of the reactions that protect us from pathologies related to aging do not occur, we accumulate damage… and eventually we die.

Today I want to share information with you about a very important molecule that we have in our bodies, of which you’ve probably never heard of. It is NAD or nicotinamide adenine dinucleotide, which is a derivative of something that we’re already familiar with, vitamin B3, also known as niacin, niacinamide or nicotinamide (soluble form). NAD is used in over 500 reactions and has a crucial role in metabolism, cellular aging, DNA repair, and gene expression.

Additionally, they intervene vitally in two very important human pathways, which we’ve already mentioned in previous blog posts, namely the sirtuin and PARP pathways.

Sirtuins are a group of 7 enzymes, specifically deacetylase, which are highly preserved from an evolutionary standpoint, from bacteria to humans. They regulate functions that influence the aging process such as mitochondria synthesis, apoptosis, autophagy, inflammation, intracellular and systemic signaling, DNA repair, etc… They’ve been called the genes of longevity.

PARP (Poly-ADP-Ribose polymerase) are a family of polymerase involved in DNA repair, genomic stability, and programmed cell death.

These very important processes I have just mentioned do not occur if there is no NAD, which leads us to accumulate damage, age, and die.

That’s how important NAD is. Additionally, NAD levels drop as we age. In fact, it plays a role in the so called “Hallmarks of aging“.

NAD comes in two forms: NAD+ and NADH. NAD+ accepts electrons from other molecules, becoming NADH, and NADH donates an electron to another molecule, becoming NAD.

Why do its levels decline over the years?

Like most things in our bodies, it’s a balance between production and degradation; in this case, it is simple: not only does the body produce less, but it also degrades more.

As shown in this chart, there are two fundamental synthesis pathways:

The de novo pathway and the salvage pathway.

• The de novo pathway synthesizes NAD from the tryptophan we consume in our diet, but this pathway is not very efficient.
• The salvage pathway effectively uses as precursors recycled parts of the use of NAD as cofactors in various reactions or after it has been used by sirtuins, for example. This is the main pathway of NAD production, but it is limited as we age because of the activity of the enzyme NMPT.

In addition to the decline in its production, as already mentioned, its degradation increases, as well. The previously mentioned PARP increase their activity over the years. This totally makes sense: as we age, DNA damage accumulates, and they must increase their activity to repair it, thus consuming more NAD. And there is another enzyme called CD-38, whose activity doubles or triples as we age, and this directly degrades NAD. In fact, it is believed that the benefit of treatments that seek to combat the inflammation that occurs over the years (inflammaging) comes with the fact that they decrease their activity.

What can we do to keep our NAD levels from declining over the years?

The scientific community is investigating exactly this. It is considering the possibility of increasing de novo synthesis, promoting the salvage pathway, and lowering the activity of enzymes that degrade NAD. Sounds simple, right?

Let’s see what we know so far:

• Increasing de novo synthesis: As already mentioned, this pathway is not very efficient and increasing tryptophan intake does not seem like the best option.
• Promoting the salvage pathway: This can be done in two ways. One, by providing more precursors of the salvage pathway like Nicotinamide (NAM), Nicotinamide Riboside (NR), and Nicotinamide Mononucleotide (NMN), to which we will add what we know about Niacin or Nicotinic Acid (NA), which we may see in the chart for the Preiss-Handler pathway; and two, by increasing the activity of NAMPT.
  • Niacin is a great choice. Studies show that it may increase up to 2 times the levels of NAD in 10 months, and it’s affordable. One disadvantage is that extended-release niacin is toxic to our liver, and immediate release niacin may quite often cause what is called the “Niacin Flush”, skin redness accompanied by a greater or lesser degree of itching. However, this is usually the case with the first doses, and then after the body gets used to it, it no longer happens. Moreover, niacin raises our good cholesterol (HDL) level, one of the few treatments to achieve this result. We’ll cover this topic in future blog posts.
  • NMN: it’s the most promising. As shown in the chart, it only needs a small reaction to become NAD. The problem is that to this day it is a very expensive supplement, there are no studies that tell us exactly how much NAD levels go up, and there is controversy regarding how it enters the cell.
  • NR: It seems that it may double the levels of NAD with a dose of 1 g, but we don’t know if it must be converted into Nicotinamide before becoming NAD or if it does so directly.
  • Nicotinamide: This is the soluble form of Vitamin B3. But it’s not without controversy either. It has been shown that when we take it, we inhibit SIRT1 (one of the sirtuins) for 1h, but after 8h it increases its activity. Inhibiting the activity of our sirtuins is the last thing we want, so the way to prevent this from happening is being researched. Additionally, its use and that of any of its derivatives such as NMN, NA, or NR interferes with a very important process called methylation, which is essential for neurotransmitter synthesis, creatine synthesis, choline, and DNA methylation, so whenever we supplement with these precursors, we must add another compound to prevent this interference from happening, usually TMG (trimethylglycine).
  • Increasing NAMPT activity. As we have seen, its activity drops over the years, making it difficult to convert Nicotinamide into NMN. What strategies have been shown to increase its activity? Interestingly, but it should come as no surprise, two of the most consolidated, effective, and acclaimed antiaging measures appear here: exercise and nutrition. Aerobic activity has been shown to increase its activity by 12% in young people and 28% in older adults, while strength training increases its activity by 25% and 30% respectively. Calorie restriction (CR) or calorie restriction mimetics, mentioned in these blog posts, have also been shown to increase its activity.

• The last proposed strategy is to lower the activity of enzymes that consume NAD or degrade it. I think it is clear that we have no interest in lowering the activity of our sirtuins or PARPs. But we may do so in the case of CD-38.

So far we know that a flavonoid present in dry parsley, celery, and chamomile tea, called apigenin, may lower its activity.

I hope that I have been able to convey the vital importance of NAD and maintaining its proper levels. I hope this reinforces your use of good nutrition habits, exercise, and supplementation, as I’ve provided a few more reasons as to why we should exercise, eat well, and use vitamin supplements, as is the case with B3.

BIBLIOGRAPHY

(1) Imai S, Guarente L. NAD+ and sirtuins in aging and disease. Trends Cell Biol. 2014;24(8):464-471. doi:10.1016/j.tcb.2014.04.002

(2) De Flora A, et al. Autocrine and paracrine calcium signaling by the CD38/NAD+/cyclic ADP-ribose system. Ann N Y Acad Sci. 2004;1028:176–191.

(3) Lin S-J, et al. Calorie restriction extends yeast life span by lowering the level of NADH. Genes Dev. 2004;18:12–16.

(4) Imai S, Yoshino J. The importance of NAMPT/NAD/SIRT1 in the systemic regulation of metabolism and ageing. Diabetes Obes Metab. 2013;15(Suppl 3):26–33.

(5) Satoh A, et al. The role of mammalian sirtuins in the regulation of metabolism, aging, and longevity. Handb Exp Pharmacol. 2011;206:125–162.

(6) Lin SJ, et al. Life span extension by calorie restriction in S. cerevisiae requires NAD and SIR2. Science. 2000;289:2126–2128.