12 Best Anti-Aging Supplements 2021: Guide and Research Review
If you are looking for the best anti-aging supplements, you've come to the right place. Aging, which can be defined as the “time-related deterioration of the physiological functions necessary for survival and fertility,” is a process that most people would like to slow (Source).
While aging is inevitable, increasing the human lifespan and slowing the aging process has been a focus of scientific research for decades.
Through that research, scientists have identified and validated a large number of substances and methods that have anti-aging benefits.
This article compiles research related to the anti-aging or slowing the aging process. This article will also reveal exciting new information about a variety of nutrients that may help you maintain youthful immune system function into advancing age.
Methodology: The selection or short-listing of the list below is based on the available scientific evidence retrieved from scientific database such as PubMed and scientific search engine such as Google Scholar. The article will also be updated as and when there is a newly discovered major research publication related to anti-aging.
Nutrients and Supplements
1. Curcumin (Turmeric)
Curcumin — the main active compound in turmeric — has been shown to possess powerful anti-aging properties, which are attributed to its potent antioxidant potential.
Cellular senescence occurs when cells stop dividing. As you age, senescent cells accumulate, which is believed to accelerate aging and disease progression (Trusted Source, Trusted Source).
Research demonstrates that curcumin activates certain proteins, including sirtuins and AMP-activated protein kinase (AMPK), which helps delay cellular senescence and promotes longevity (Trusted Source, Trusted Source).
Plus, curcumin has been shown to combat cellular damage and significantly increase the lifespan of fruit flies, roundworms, and mice. This compound has been shown to postpone age-related disease and alleviate age-related symptoms as well (Trusted Source, Trusted Source).
This may be why turmeric intake has been associated with a reduced risk of age-related mental decline in humans (Trusted Source).
You can increase your curcumin intake by using turmeric in recipes or taking curcumin supplements.
2. EGCG (Green Tea)
Epigallocatechin gallate (EGCG) is a well-known polyphenol compound concentrated in green tea. It offers impressive health benefits, with research supporting its use to reduce the risk of certain cancers, as well as other health conditions like heart disease (Trusted Source, Trusted Source, Trusted Source).
Among EGCG’s diverse array of potential health-promoting properties is its ability to promote longevity and protect against age-related disease development.
EGCG may slow aging by restoring mitochondrial function in cells and acting on pathways involved in aging, including the AMP-activated protein kinase signaling pathway (AMPK).
It also induces autophagy, the process by which your body removes damaged cellular material (Trusted Source).
Green tea intake has been associated with a reduced risk of all-cause mortality, diabetes, stroke, and heart-disease-related death. Plus, animal studies have shown that it can protect against skin aging and wrinkles caused by ultraviolet (UV) light (Trusted Source, Trusted Source, Trusted Source).
EGCG can be consumed by drinking green tea or taking concentrated supplements.
Curcumin — the main active compound in turmeric — has been shown to possess powerful anti-aging properties, which are attributed to its potent antioxidant potential.
Cellular senescence occurs when cells stop dividing. As you age, senescent cells accumulate, which is believed to accelerate aging and disease progression (Trusted Source, Trusted Source).
Research demonstrates that curcumin activates certain proteins, including sirtuins and AMP-activated protein kinase (AMPK), which helps delay cellular senescence and promotes longevity (Trusted Source, Trusted Source).
Plus, curcumin has been shown to combat cellular damage and significantly increase the lifespan of fruit flies, roundworms, and mice. This compound has been shown to postpone age-related disease and alleviate age-related symptoms as well (Trusted Source, Trusted Source).
This may be why turmeric intake has been associated with a reduced risk of age-related mental decline in humans (Trusted Source).
You can increase your curcumin intake by using turmeric in recipes or taking curcumin supplements.
2. EGCG (Green Tea)
Epigallocatechin gallate (EGCG) is a well-known polyphenol compound concentrated in green tea. It offers impressive health benefits, with research supporting its use to reduce the risk of certain cancers, as well as other health conditions like heart disease (Trusted Source, Trusted Source, Trusted Source).
Among EGCG’s diverse array of potential health-promoting properties is its ability to promote longevity and protect against age-related disease development.
EGCG may slow aging by restoring mitochondrial function in cells and acting on pathways involved in aging, including the AMP-activated protein kinase signaling pathway (AMPK).
It also induces autophagy, the process by which your body removes damaged cellular material (Trusted Source).
Green tea intake has been associated with a reduced risk of all-cause mortality, diabetes, stroke, and heart-disease-related death. Plus, animal studies have shown that it can protect against skin aging and wrinkles caused by ultraviolet (UV) light (Trusted Source, Trusted Source, Trusted Source).
EGCG can be consumed by drinking green tea or taking concentrated supplements.
3. Pu-erh Tea Extract
Pu-erh tea, made from select leaves of Camellia sinensis, has a long history of use in ancient Chinese medicine for anti-aging and preventing infections (Lv 2014; Zhang 2012; Chu 2011). Pu-erh tea is rich in polyphenols and other bioactive molecules, including theabrownins, a unique group of compounds developed during the post-fermentation process (Lee 2013). Laboratory, animal, and clinical studies have demonstrated the ability of Pu-erh tea extract to help improve multiple features of immune senescence.
In senescence-accelerated mice (a model for aging), supplementation with Pu-erh tea extract markedly increased fractions of naïve T cells, cytotoxic T cells, and NK cells. In addition, elevated levels of the inflammatory cytokine IL-6 fell by 43%. Based on these results, the authors concluded that long-term consumption of Pu-erh tea may increase resistance to infection and cancer in aging individuals (Zhang 2012).
In a randomized controlled trial in 90 individuals with increased susceptibility to chronic low-level inflammation due to metabolic syndrome, Pu-erh tea extract supplementation plus diet and lifestyle advice was compared with diet and lifestyle advice alone. In the pu-erh tea extract group, levels of the inflammatory markers C-reactive protein, tumor necrosis factor-alpha, and IL-6 significantly decreased, while levels of IL-10, an anti-inflammatory molecule, increased; there were no significant changes in levels of these markers in the group receiving only diet and lifestyle advice (Chu 2011; Moore 2001).
In a laboratory study, Pu-erh tea inhibited proliferation and induced programmed cell death (apoptosis) in cancer cells. In an animal component of this study, mice treated with Pu-erh tea had reduced tumor volumes and fewer lymph node metastases than untreated mice. In addition, levels of IL-6, IL-12, and tumor necrosis factor-alpha were lower in Pu-erh-treated mice than in control mice. In this study, higher doses of pu-erh tea produced greater anti-cancer effects (Zhao 2014).
Pu-erh tea, made from select leaves of Camellia sinensis, has a long history of use in ancient Chinese medicine for anti-aging and preventing infections (Lv 2014; Zhang 2012; Chu 2011). Pu-erh tea is rich in polyphenols and other bioactive molecules, including theabrownins, a unique group of compounds developed during the post-fermentation process (Lee 2013). Laboratory, animal, and clinical studies have demonstrated the ability of Pu-erh tea extract to help improve multiple features of immune senescence.
In senescence-accelerated mice (a model for aging), supplementation with Pu-erh tea extract markedly increased fractions of naïve T cells, cytotoxic T cells, and NK cells. In addition, elevated levels of the inflammatory cytokine IL-6 fell by 43%. Based on these results, the authors concluded that long-term consumption of Pu-erh tea may increase resistance to infection and cancer in aging individuals (Zhang 2012).
In a randomized controlled trial in 90 individuals with increased susceptibility to chronic low-level inflammation due to metabolic syndrome, Pu-erh tea extract supplementation plus diet and lifestyle advice was compared with diet and lifestyle advice alone. In the pu-erh tea extract group, levels of the inflammatory markers C-reactive protein, tumor necrosis factor-alpha, and IL-6 significantly decreased, while levels of IL-10, an anti-inflammatory molecule, increased; there were no significant changes in levels of these markers in the group receiving only diet and lifestyle advice (Chu 2011; Moore 2001).
In a laboratory study, Pu-erh tea inhibited proliferation and induced programmed cell death (apoptosis) in cancer cells. In an animal component of this study, mice treated with Pu-erh tea had reduced tumor volumes and fewer lymph node metastases than untreated mice. In addition, levels of IL-6, IL-12, and tumor necrosis factor-alpha were lower in Pu-erh-treated mice than in control mice. In this study, higher doses of pu-erh tea produced greater anti-cancer effects (Zhao 2014).
4. CoQ10
Coenzyme Q10 (CoQ10) is an antioxidant that your body produces. It plays essential roles in energy production and protects against cellular damage (Trusted Source).
Research suggests that levels of CoQ10 decline as you age, and supplementing with it has been shown to improve certain aspects of health in older individuals.
For example, a study in 443 older adults demonstrated that supplementing with CoQ10 and selenium over 4 years improved their overall quality of life, reduced hospital visits, and slowed the deterioration of physical and mental performance (Trusted Source).
CoQ10 supplements help reduce oxidative stress, a condition characterized by an accumulation of free radicals and other reactive molecules that accelerates the aging process and onset of age-related disease (Trusted Source, Trusted Source).
Though CoQ10 shows promise as an anti-aging supplement, more evidence is needed before it can be recommended as a natural way to delay aging.
Be sure to consult a trusted healthcare professional before giving it a try.
5. Collagen
Collagen is promoted as a fountain of youth for its potential to reduce the appearance of skin aging.
It’s an integral component of your skin that helps maintain skin structure. As you age, collagen production slows, leading to collagen loss in the skin that accelerates signs of aging like wrinkles.
Some research suggests that supplementing with collagen may reduce signs of aging, including wrinkles and dry skin.
For example, a 2019 study in 72 women demonstrated that taking a supplement that contained 2.5 grams of collagen — along with several other ingredients, including biotin — per day for 12 weeks significantly improved skin hydration, roughness, and elasticity (Trusted Source).
Another study in 114 women found that treatment with 2.5 grams of collagen peptides for 8 weeks significantly reduced eye wrinkles and increased collagen levels in the skin (Trusted Source).
Though these results are promising, keep in mind that many collagen studies are funded by companies that manufacture collagen products, which may influence study results.
Many types of collagen supplements are on the market, including powders and capsules.
6. Zinc
Zinc is an essential trace mineral that is critical to healthy immune function. Zinc deficiency is common in older individuals, and causes changes in immune function that resemble those seen in immune senescence (Cabrera 2015; Maywald 2015). Immunological alterations associated with zinc deficiency include diminished thymus function, decreased antibody response to vaccines, and impaired function of phagocytic and NK cells (Haase 2009; Cabrera 2015).
In a study in healthy older volunteers, daily intake of 45 mg zinc for one year resulted in a 67% reduction versus placebo in incidence of infections. Levels of tumor necrosis factor-alpha, an inflammatory cytokine, were also greatly reduced in those taking zinc (Prasad 2007). In a study of older individuals in nursing homes, residents with normal zinc levels had a significantly lower incidence of pneumonia compared with zinc-deficient individuals. Zinc-replete individuals also had shorter pneumonia duration and 50% lower usage of antibiotics, as well as lower all-cause mortality (Meydani 2007). A controlled clinical trial in aged individuals showed supplementation with 45 mg zinc per day for six months decreased plasma markers of inflammation, including IL-6 and C-reactive protein (Bao 2010).
Combining zinc with other important vitamins and minerals may also aid immune function. In a randomized controlled trial that enrolled 42 subjects between 55 and 75 years of age, those who took a multivitamin/mineral supplement containing 10 mg zinc and 1,000 mg vitamin C, along with other vitamins and minerals, for 12 weeks experienced fewer self-reported sick days and less severe symptoms than those who took placebo. The number of sick days decreased by nearly 65% with supplement use (Fantacone 2020).
7. NAC (N-Acetyl Cysteine)
Cysteine is a semi-essential amino acid. It’s considered semi-essential because your body can produce it from other amino acids, namely methionine and serine. It becomes essential only when the dietary intake of methionine and serine is low.
Cysteine is found in most high-protein foods, such as chicken, turkey, yogurt, cheese, eggs, sunflower seeds and legumes.
N-acetyl cysteine (NAC) is a supplement form of cysteine.
Consuming adequate cysteine and NAC is important for a variety of health reasons — including replenishing the most powerful antioxidant in your body, glutathione. These amino acids also help with chronic respiratory conditions, fertility and brain health.
NAC is valued primarily for its role in antioxidant production. Along with two other amino acids — glutamine and glycine — NAC is needed to make and replenish glutathione.
Glutathione is one of the body’s most important antioxidants, which helps neutralize free radicals that can damage cells and tissues in your body.
It’s essential for immune health and fighting cellular damage. Some researchers believe it may even contribute to longevity (Trusted Source).
Its antioxidant properties are also important for combatting numerous other ailments caused by oxidative stress, such as heart disease, infertility and some psychiatric conditions (Trusted Source).
In a controlled clinical trial in 262 individuals at high risk of influenza (flu) and flu-like illness, NAC supplementation at a dosage of 600 mg twice daily for six months resulted in a significant decrease in frequency and severity of flu and flu symptoms, such as cough, sore throat, headache, and muscle and joint pain. NAC’s ability to protect against flu symptoms was especially evident during the winter season. Of those who tested positive for influenza virus infection during the study, only 25% in the NAC group developed symptomatic illness compared with 79% in the placebo group (De Flora 1997).
This same NAC dosage in dialysis patients, over eight weeks, resulted in marked reductions in levels of inflammatory markers, including C-reactive protein, tumor necrosis factor-alpha, and IL-6 (Purwanto 2012).
NAC is likely safe for adults when provided as a prescription medication. However, high amounts may cause nausea, vomiting, diarrhea and constipation (Trusted Source).
When inhaled, it can cause swelling in the mouth, runny nose, drowsiness and chest tightness.
People with bleeding disorders or taking blood thinning medications should not take NAC, as it may slow blood clotting (Trusted Source).
NAC has an unpleasant smell that makes it hard to consume. If you choose to take it, consult with your doctor first.
8. Resveratrol
Online Shopping Guide
Before adding a new supplement to your routine, discuss its use with your healthcare provider, especially if you have an underlying health condition or are taking medication.
While many of the anti-aging supplements may be available in your local stores, it may be more convenient or affordable to shop for them online on Amazon (US):
When inhaled, it can cause swelling in the mouth, runny nose, drowsiness and chest tightness.
People with bleeding disorders or taking blood thinning medications should not take NAC, as it may slow blood clotting (Trusted Source).
NAC has an unpleasant smell that makes it hard to consume. If you choose to take it, consult with your doctor first.
8. Resveratrol
Resveratrol is a polyphenol in grapes, berries, peanuts, and red wine that may promote longevity by activating certain genes called sirtuins. It has been shown to increase the lifespan of fruit flies, yeasts, and nematodes (Trusted Source).
9. Garlic
9. Garlic
Garlic, well known for its ability to improve cardiovascular risk factors, also has immune-modulating and immunostimulatory properties, as well as anti-tumor effects (Ebrahimi 2013; Purev 2012; Kyo 2001).
A detailed review of data from published clinical trials found garlic supplements significantly reduce the number, duration, and severity of upper respiratory tract infections. This review also found garlic supplements stimulate immune function by increasing macrophage activity, numbers of NK cells, and production of T and B cells (Ried 2016). In a clinical trial, 120 healthy participants, 21–50 years old, were assigned to use 2.56 g aged garlic extract or placebo daily for 90 days during cold and flu season. Garlic supplementation was associated with reduced cold and flu severity, as well as increased cytotoxic T-cell and NK-cell proliferation and activity (Percival 2016). In animal research, garlic has been shown to increase antibody production and enhance the cell-killing activity of macrophages, cytotoxic T cells, and NK cells (Ghazanfari 2000). Other animal research suggests aged garlic extract may prevent immune suppression associated with psychological stress (Kyo 1999).
Interestingly, garlic has also been demonstrated to suppress the overactive immune response associated with allergic reactions. Data from experimental studies indicate aged garlic extract may reduce histamine release and modify the function of immune cells involved in allergic reactions (Kyo 2001).
Interestingly, garlic has also been demonstrated to suppress the overactive immune response associated with allergic reactions. Data from experimental studies indicate aged garlic extract may reduce histamine release and modify the function of immune cells involved in allergic reactions (Kyo 2001).
Test-tube and rodent studies have also shown that supplementing with garlic may prevent UV-light-induced skin aging and wrinkles (Trusted Source).
Whey is the liquid separated from the curds during the cheese making process. Products derived from whey have demonstrated immune-modulating properties (Krissansen 2007; Rusu 2009). Whey protein is especially rich in precursor amino acids involved in the synthesis of glutathione, a powerful free radical scavenger with anti-inflammatory properties. Glutathione is essential for both innate and adaptive immunity (Krissansen 2007; Kloek 2011; Kent 2003; Micke 2001). (N-acetylcysteine, described earlier, is also a glutathione precursor.)
A pilot study compared the effects of whey protein and soy protein on vaccine responsiveness in 17 healthy senior citizens (Freeman 2010). The participants were randomly assigned to consume either whey protein or soy protein for four weeks. They then received the pneumococcal vaccine and continued protein supplementation for four weeks after vaccination. Compared with those who received soy protein, people who received whey protein exhibited a more robust antibody response to 12 of 14 types of pneumococcal bacteria, including the four most harmful bacterial types. The investigators concluded, “ Whey protein supplementation is a promising supplement to stimulate the immune response to vaccine in senior citizens and possibly to counteract [immune senescence] while larger studies are warranted.”
In another clinical trial in 12 healthy volunteers, a single dose of a whey extract was a more effective immune activator than placebo, rapidly increasing phagocytic (microbe-engulfing) activity of certain immune cells and mobilizing new NK cells into circulation (Jensen 2012). In a study in cultured neutrophils, whey protein extract had no immediate effect but instead had a priming effect, heightening neutrophil activity 24 hours later (Rusu 2009).
While some studies suggest that taking certain supplements, hormone replacement or even stem cells may help slow aging, you can't do away with healthy practices as mentioned above. Strategies that are implemented as a combination are better than a single strategy alone.
Mediterranean Diet
The Mediterranean diet is a dietary pattern based on foods and drinks traditionally consumed by people in the region surrounding the Mediterranean Sea (Oldways 2016). The Mediterranean diet has been shown to protect against several age- and inflammation-related conditions including diabetes, atherosclerosis, obesity, cancers, and neurodegenerative diseases. The Mediterranean diet is primarily characterized by inclusion of olive oil, fruits, vegetables, legumes, whole grains, nuts, and seeds; with moderate amounts of fish, poultry, cheese, yogurt, and eggs; limited inclusion of red meat, cured meat products, and foods rich in refined sugars; and low-to-moderate alcohol intake, usually in the form of red wine consumed with meals (Casas 2014; Estruch 2010).
In a 2014 review of 17 clinical trials, greater adherence to a Mediterranean dietary pattern was associated with significantly reduced levels of interleukin (IL)-6 and high-sensitivity C-reactive protein, two important markers of inflammation (Schwingshackl 2014; Coventry 2009; Ershler 2000; US Department of Health and Human Services 2015).
Exercise
Regular moderate-intensity exercise can strengthen resistance to infection and improve immune system function. Single bouts of moderate-intensity exercise have even been used to improve response to vaccines. On the other hand, prolonged, excessive high-intensity exercise (ie, over-training) temporarily suppresses immune function and increases vulnerability to infection (Simpson 2015; Gleeson 2013; Zheng 2015).
Several human studies have indicated that moderate exercise may combat immune senescence (de Araujo 2013; Simpson 2011; Simpson 2010; Spielmann 2011; Woods 2009). In a study in sedentary older adults, participants randomized to 10 months of moderate cardiovascular exercise exhibited improvements in antibody responses to influenza vaccine compared with elderly individuals who only engaged in flexibility and balance exercises (Woods 2009).
In a study in elderly women, two years of regular physical activity increased production of IL-2—an important regulator of immune response that ordinarily decreases with age (Drela 2004). A 2011 study demonstrated that aerobic fitness is associated with reduced accumulation of senescent T cells (Spielmann 2011).
The effects of high levels of physical activity were evaluated in an observational cohort study of 125 adults aged 55 to 79 years who are master cyclists. Compared with 75 age-matched older adults who do not routinely exercise, the cyclists were shown to have more markers of a robust immune system. Older, physically active adults had significantly lower levels of immune senescence markers, including lower Th17 cell polarization and higher proportions of regulatory B cells. Lower levels of Th17 cells, which are T cells that have been shown to suppress the immune system, together with higher levels of regulatory B cells, may help decrease the risk of age-associated inflammatory autoimmune disease. Older adult cyclists also had cytokine signatures that promote thymus health—the key organ in which T cells mature. Furthermore, T-cell levels in the cyclists were comparable with those of much younger adults (aged 20 to 39 years). In contrast, inactive older adults had lower levels of T cells compared with both older adult cyclists and younger adults. Taken together, these results suggest that maintaining physical activity may delay immune senescence (Duggal 2018).
Stress Management
Chronic stress causes dysregulation of innate and adaptive immune responses by promoting persistent systemic inflammation and suppressing immune cells (Morey 2015; Dhabhar 2014). When sustained stress diminishes immune function, it can allow latent viruses such as cytomegalovirus to escape immune system control. Frequent reactivation of latent viruses can then further strain the immune system (Morey 2015). Chronic stress, and the accompanying chronic elevation of the stress-induced adrenal hormone, cortisol, appear to contribute to immune senescence (Bosch 2009; Bauer 2015). In fact, the ratio of cortisol to another adrenal hormone, dehydroepiandrosterone (DHEA), may be an important determinant of immune senescence (Bauer 2008).
In studies on patients with early-stage breast cancer, stress management interventions have been shown to improve cellular immune function and reverse pro-inflammatory gene expression in circulating immune cells (Antoni 2012; McGregor 2004). Stress management training in patients with rheumatoid arthritis resulted in decreased levels of stress-induced IL-8—an inflammatory cytokine (de Brouwer 2013).
Sleep
Lack of sleep can weaken immune function and increase susceptibility to respiratory infections, including the common cold, and chronic lack of sleep may be associated with an increased risk of death (Prather 2015; Ibarra-Coronado 2015; Wilder-Smith 2013; Aldabal 2011). Sleep deprivation is associated with elevated cortisol levels, as well as higher daytime levels of inflammatory cytokines including IL-1, IL-6, and tumor necrosis factor-alpha (Aldabal 2011; Hirotsu 2015). A study in individuals aged 61‒86 found even a single night of partial sleep deprivation induced patterns of gene activation associated with biological aging (Carroll 2016).
The adverse effects of poor sleep include functional changes in regulatory T cells and other cells of the adaptive immune system, as well as reduced numbers of NK cells and T and B cells (Zuppa 2015; Bollinger 2009).
Reduced sleep has been shown to alter the balance between antibody-mediated and cell-mediated immunity (Ganz 2012). In one study, participants allowed regular sleep the night after vaccines had markedly superior long-term antibody responses compared with those who stayed awake that night. Another study showed sleep-deprived individuals had a significantly lower antibody response 10 days after immunization than those who had normal sleep (Lange 2003; Spiegel 2002).
Caloric Restriction
The goal of caloric restriction is to reduce total caloric intake while maintaining optimal nutrition. This may be best accomplished by eating a diet primarily composed of low-calorie, nutrient-dense foods such as vegetables, fruits, legumes, nuts and seeds, and whole grains; limiting intake of animal products; and avoiding calorie-dense, nutrient-poor foods (Rizza 2014). Caloric restriction in animals has been shown to prolong lifespan and delay aging, and to confer a more youthful profile of T cells (Ahmed 2009; Fernandes 1997; Michan 2014).
In humans, long-term caloric restriction results in metabolic changes that reduce the risk of a number of age-related diseases including type 2 diabetes, cardiovascular disease, and cancer (Steven 2015; Rizza 2014; Bales 2013; Lefevre 2009; Meyer 2006; Fontana 2004; Stein 2012). In a clinical study, six months of caloric restriction significantly improved the ability of T cells to reproduce in response to foreign antigens (Ahmed 2009).
Studies in animal models have demonstrated that caloric restriction can improve multiple aspects of immune activity, particularly T-cell function (Jolly 2004; Messaoudi 2006; Nikolich-Zugich 2005). In a study in mice, caloric restriction was shown to maintain youthful function of the thymus gland and reduce immune senescence during aging. Compared with mice fed freely, calorie-restricted mice had greater proliferation and diversity of T cells (Yang 2009).
10. Molecular Hydrogen
The ability of molecular hydrogen (H2) to protect the DNA and the mitochondria from oxidative damage may have beneficial effects on chronic diseases and cancer. But perhaps it could help slow down or reverse the aging process itself. A couple of cellular studies give us some interesting clues [Ref, R].
It was already discovered that hydrogen can prolong the life of stem cells by reducing oxidative stress [Ref].
A hydrogen-rich environment reduced both oxidative stress and aging in cells. Some scientists think
that drinking hydrogen water could increase longevity in humans (Circ J. 2016).
11. L-Citrulline and Olive Leaf Extract
L-citrulline is a naturally occurring amino acid found in some foods like watermelons and is also produced naturally by the body. Citrulline can promote heart health by widening your blood vessels. It can also improve your exercise performance and may play a role in muscle building (Curr Opin Clin Nutr Metab Care. 2017). After citrulline is consumed, some is converted to another amino acid called arginine. Arginine is converted into a molecule called nitric oxide, which causes vasodilation of blood vessels by relaxing the smooth muscle cells that constrict them (Nitric Oxide. 2015). Though research has found both arginine and citrulline to boost levels of nitric oxide (NO) in the body, most recent research—like this The Journal of Nutrition study—shows that citrulline actually delivers the most benefit. The body use arginine for a variety of functions, so it doesn’t use all of the arginine it absorbs to produce NO. Plus, unlike citrulline, higher doses of arginine have been linked to gastrointestinal problems. Because it tends to be poorly absorbed, arginine can even lead to diarrhea when consumed in large amounts.
Olive leaf extract is a natural source of wellness with therapeutic properties that are:
12. Whey ProteinThe ability of molecular hydrogen (H2) to protect the DNA and the mitochondria from oxidative damage may have beneficial effects on chronic diseases and cancer. But perhaps it could help slow down or reverse the aging process itself. A couple of cellular studies give us some interesting clues [Ref, R].
It was already discovered that hydrogen can prolong the life of stem cells by reducing oxidative stress [Ref].
A hydrogen-rich environment reduced both oxidative stress and aging in cells. Some scientists think
that drinking hydrogen water could increase longevity in humans (Circ J. 2016).
11. L-Citrulline and Olive Leaf Extract
L-citrulline is a naturally occurring amino acid found in some foods like watermelons and is also produced naturally by the body. Citrulline can promote heart health by widening your blood vessels. It can also improve your exercise performance and may play a role in muscle building (Curr Opin Clin Nutr Metab Care. 2017). After citrulline is consumed, some is converted to another amino acid called arginine. Arginine is converted into a molecule called nitric oxide, which causes vasodilation of blood vessels by relaxing the smooth muscle cells that constrict them (Nitric Oxide. 2015). Though research has found both arginine and citrulline to boost levels of nitric oxide (NO) in the body, most recent research—like this The Journal of Nutrition study—shows that citrulline actually delivers the most benefit. The body use arginine for a variety of functions, so it doesn’t use all of the arginine it absorbs to produce NO. Plus, unlike citrulline, higher doses of arginine have been linked to gastrointestinal problems. Because it tends to be poorly absorbed, arginine can even lead to diarrhea when consumed in large amounts.
Olive leaf extract is a natural source of wellness with therapeutic properties that are:
- gastroprotective (protects digestive system)
- neuroprotective (protects central nervous system)
- antimicrobial (inhibits microorganism growth)
- anticancer (reduces risk of cancer)
- anti-inflammatory (reduces risk of inflammation)
- antinociceptive (reduces pain stimuli)
- antioxidant (prevents oxidation or cell damage)
Whey is the liquid separated from the curds during the cheese making process. Products derived from whey have demonstrated immune-modulating properties (Krissansen 2007; Rusu 2009). Whey protein is especially rich in precursor amino acids involved in the synthesis of glutathione, a powerful free radical scavenger with anti-inflammatory properties. Glutathione is essential for both innate and adaptive immunity (Krissansen 2007; Kloek 2011; Kent 2003; Micke 2001). (N-acetylcysteine, described earlier, is also a glutathione precursor.)
A pilot study compared the effects of whey protein and soy protein on vaccine responsiveness in 17 healthy senior citizens (Freeman 2010). The participants were randomly assigned to consume either whey protein or soy protein for four weeks. They then received the pneumococcal vaccine and continued protein supplementation for four weeks after vaccination. Compared with those who received soy protein, people who received whey protein exhibited a more robust antibody response to 12 of 14 types of pneumococcal bacteria, including the four most harmful bacterial types. The investigators concluded, “ Whey protein supplementation is a promising supplement to stimulate the immune response to vaccine in senior citizens and possibly to counteract [immune senescence] while larger studies are warranted.”
In another clinical trial in 12 healthy volunteers, a single dose of a whey extract was a more effective immune activator than placebo, rapidly increasing phagocytic (microbe-engulfing) activity of certain immune cells and mobilizing new NK cells into circulation (Jensen 2012). In a study in cultured neutrophils, whey protein extract had no immediate effect but instead had a priming effect, heightening neutrophil activity 24 hours later (Rusu 2009).
Diet and Lifestyle
The best way to promote longevity and overall health is to engage in healthy practices like consuming a nutritious diet, engaging in regular exercise and reducing stress.
The Mediterranean diet is a dietary pattern based on foods and drinks traditionally consumed by people in the region surrounding the Mediterranean Sea (Oldways 2016). The Mediterranean diet has been shown to protect against several age- and inflammation-related conditions including diabetes, atherosclerosis, obesity, cancers, and neurodegenerative diseases. The Mediterranean diet is primarily characterized by inclusion of olive oil, fruits, vegetables, legumes, whole grains, nuts, and seeds; with moderate amounts of fish, poultry, cheese, yogurt, and eggs; limited inclusion of red meat, cured meat products, and foods rich in refined sugars; and low-to-moderate alcohol intake, usually in the form of red wine consumed with meals (Casas 2014; Estruch 2010).
In a 2014 review of 17 clinical trials, greater adherence to a Mediterranean dietary pattern was associated with significantly reduced levels of interleukin (IL)-6 and high-sensitivity C-reactive protein, two important markers of inflammation (Schwingshackl 2014; Coventry 2009; Ershler 2000; US Department of Health and Human Services 2015).
Exercise
Regular moderate-intensity exercise can strengthen resistance to infection and improve immune system function. Single bouts of moderate-intensity exercise have even been used to improve response to vaccines. On the other hand, prolonged, excessive high-intensity exercise (ie, over-training) temporarily suppresses immune function and increases vulnerability to infection (Simpson 2015; Gleeson 2013; Zheng 2015).
Several human studies have indicated that moderate exercise may combat immune senescence (de Araujo 2013; Simpson 2011; Simpson 2010; Spielmann 2011; Woods 2009). In a study in sedentary older adults, participants randomized to 10 months of moderate cardiovascular exercise exhibited improvements in antibody responses to influenza vaccine compared with elderly individuals who only engaged in flexibility and balance exercises (Woods 2009).
In a study in elderly women, two years of regular physical activity increased production of IL-2—an important regulator of immune response that ordinarily decreases with age (Drela 2004). A 2011 study demonstrated that aerobic fitness is associated with reduced accumulation of senescent T cells (Spielmann 2011).
The effects of high levels of physical activity were evaluated in an observational cohort study of 125 adults aged 55 to 79 years who are master cyclists. Compared with 75 age-matched older adults who do not routinely exercise, the cyclists were shown to have more markers of a robust immune system. Older, physically active adults had significantly lower levels of immune senescence markers, including lower Th17 cell polarization and higher proportions of regulatory B cells. Lower levels of Th17 cells, which are T cells that have been shown to suppress the immune system, together with higher levels of regulatory B cells, may help decrease the risk of age-associated inflammatory autoimmune disease. Older adult cyclists also had cytokine signatures that promote thymus health—the key organ in which T cells mature. Furthermore, T-cell levels in the cyclists were comparable with those of much younger adults (aged 20 to 39 years). In contrast, inactive older adults had lower levels of T cells compared with both older adult cyclists and younger adults. Taken together, these results suggest that maintaining physical activity may delay immune senescence (Duggal 2018).
Stress Management
Chronic stress causes dysregulation of innate and adaptive immune responses by promoting persistent systemic inflammation and suppressing immune cells (Morey 2015; Dhabhar 2014). When sustained stress diminishes immune function, it can allow latent viruses such as cytomegalovirus to escape immune system control. Frequent reactivation of latent viruses can then further strain the immune system (Morey 2015). Chronic stress, and the accompanying chronic elevation of the stress-induced adrenal hormone, cortisol, appear to contribute to immune senescence (Bosch 2009; Bauer 2015). In fact, the ratio of cortisol to another adrenal hormone, dehydroepiandrosterone (DHEA), may be an important determinant of immune senescence (Bauer 2008).
In studies on patients with early-stage breast cancer, stress management interventions have been shown to improve cellular immune function and reverse pro-inflammatory gene expression in circulating immune cells (Antoni 2012; McGregor 2004). Stress management training in patients with rheumatoid arthritis resulted in decreased levels of stress-induced IL-8—an inflammatory cytokine (de Brouwer 2013).
Sleep
Lack of sleep can weaken immune function and increase susceptibility to respiratory infections, including the common cold, and chronic lack of sleep may be associated with an increased risk of death (Prather 2015; Ibarra-Coronado 2015; Wilder-Smith 2013; Aldabal 2011). Sleep deprivation is associated with elevated cortisol levels, as well as higher daytime levels of inflammatory cytokines including IL-1, IL-6, and tumor necrosis factor-alpha (Aldabal 2011; Hirotsu 2015). A study in individuals aged 61‒86 found even a single night of partial sleep deprivation induced patterns of gene activation associated with biological aging (Carroll 2016).
The adverse effects of poor sleep include functional changes in regulatory T cells and other cells of the adaptive immune system, as well as reduced numbers of NK cells and T and B cells (Zuppa 2015; Bollinger 2009).
Reduced sleep has been shown to alter the balance between antibody-mediated and cell-mediated immunity (Ganz 2012). In one study, participants allowed regular sleep the night after vaccines had markedly superior long-term antibody responses compared with those who stayed awake that night. Another study showed sleep-deprived individuals had a significantly lower antibody response 10 days after immunization than those who had normal sleep (Lange 2003; Spiegel 2002).
Caloric Restriction
The goal of caloric restriction is to reduce total caloric intake while maintaining optimal nutrition. This may be best accomplished by eating a diet primarily composed of low-calorie, nutrient-dense foods such as vegetables, fruits, legumes, nuts and seeds, and whole grains; limiting intake of animal products; and avoiding calorie-dense, nutrient-poor foods (Rizza 2014). Caloric restriction in animals has been shown to prolong lifespan and delay aging, and to confer a more youthful profile of T cells (Ahmed 2009; Fernandes 1997; Michan 2014).
In humans, long-term caloric restriction results in metabolic changes that reduce the risk of a number of age-related diseases including type 2 diabetes, cardiovascular disease, and cancer (Steven 2015; Rizza 2014; Bales 2013; Lefevre 2009; Meyer 2006; Fontana 2004; Stein 2012). In a clinical study, six months of caloric restriction significantly improved the ability of T cells to reproduce in response to foreign antigens (Ahmed 2009).
Studies in animal models have demonstrated that caloric restriction can improve multiple aspects of immune activity, particularly T-cell function (Jolly 2004; Messaoudi 2006; Nikolich-Zugich 2005). In a study in mice, caloric restriction was shown to maintain youthful function of the thymus gland and reduce immune senescence during aging. Compared with mice fed freely, calorie-restricted mice had greater proliferation and diversity of T cells (Yang 2009).
Wrapping It Up
In real medicine, results are not guaranteed and there are no cure-alls. Real research is published in peer-reviewed journals, and you can search the journals via PubMed or Google Scholar.
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Online Shopping Guide
Before adding a new supplement to your routine, discuss its use with your healthcare provider, especially if you have an underlying health condition or are taking medication.
While many of the anti-aging supplements may be available in your local stores, it may be more convenient or affordable to shop for them online on Amazon (US):
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