No magic, just research-backed essential nutrients in synergy

A Review by Lucía Méndez and Isabel Medina, published 2021 April 22. Read the full review

"It has been reported that the combination of these nutraceuticals can lead to three-fold increases in glutathione peroxidase activity, two-fold increases in plasma antioxidant capacity, decreases of 50–100% in lipid peroxidation, protein carbonylation, and urinary 8-isoprotanes, as well as 50–200% attenuation of common inflammation biomarkers, among other effects, as compared to their individual capacities."

Abstract

Polyphenols and omega-3 polyunsaturated fatty acids from fish oils, i.e., eicosapentaenoic and docosahexaenoic acids, are well-recognized nutraceuticals, and their single antioxidant and anti-inflammatory properties have been demonstrated in several studies found in the literature. It has been reported that the combination of these nutraceuticals can lead to three-fold increases in glutathione peroxidase activity, two-fold increases in plasma antioxidant capacity, decreases of 50–100% in lipid peroxidation, protein carbonylation, and urinary 8-isoprotanes, as well as 50–200% attenuation of common inflammation biomarkers, among other effects, as compared to their individual capacities. Therefore, the adequate combination of those bioactive food compounds and their single properties should offer a powerful tool for the design of successfully nutritional interventions for the prevention and palliation of a plethora of human metabolic diseases, frequently diet-induced, whose etiology and progression are characterized by redox homeostasis disturbances and a low-grade of chronic inflammation. However, the certain mechanisms behind their biological activities, in vivo interaction (both between them and other food compounds), and their optimal doses and consumption are not well-known yet. Therefore, we review here the recent evidence accumulated during the last decade about the cooperative action between polyphenols and fish oils against diet-related metabolic alterations, focusing on the mechanisms and pathways described and the effects reported. The final objective is to provide useful information for strategies for personalized nutrition based on these nutraceuticals.

A Review by Mario Pagliaro, Daniela Maria Pizzone, Antonino Scurria, Claudia Lino, Emilia Paone, Francesco Mauriello, Rosaria Ciriminna, published February 2021. Read the full review

"...it is now increasingly understood that natural polyphenols present in marine oils play an essential role in protecting omega-3 lipids from oxidation and autooxidation ensuring that no pro-inflammatory products are formed after intake as it often happens with assumption of refined omega-3 concentrates."

Abstract

Thanks to the pioneering studies of Østerud and co-workers it is now increasingly understood that natural polyphenols present in marine oils play an essential role in protecting omega-3 lipids from oxidation and autooxidation ensuring that no pro-inflammatory products are formed after intake as it often happens with assumption of refined omega-3 concentrates. Strong antioxidants exerting multiple biological functions, olive biophenols are ideally suited to functionalize marine oils creating a synergy which has the potential to foster public health across the world. This study identifies suitable avenues to advance the sustainable production of health-beneficial formulations based on newly obtained natural marine oils and olive phenolic extracts. Important educational outcomes for bioeconomy educators conclude the study.

A Review by Thais Keiko Siroma, David Johane Machate, Verônica Assalin Zorgetto-Pinheiro, Priscila Silva Figueiredo, Gabriela Marcelino, Priscila Aiko Hiane, Danielle Bogo, Arnildo Pott, Elenir Rose Jardim Cury, Rita de Cássia Avellaneda Guimarães, Marcelo Luiz Brandão Vilela, Rosângela dos Santos Ferreira, Valter Aragão do Nascimento, published 2021 January 17. Read the full review

"Due to the synergistic actions of the polyphenols and ω-3 PUFAs, some products that are found, like fish and vegetables, and their by-products can potentially improve and control obesity and its RMDs as anti-glucose tolerance, anti-oxidative, anti-atherosclerosis, anti-inflammation, anti-weight gain, hepato-protective, vascular-protective, cardiovascular-protective, anti-hypertension, anti-diabetic effects, thus improving the human health."

Abstract

Obesity is associated with the leading causes of death in the worldwide. On the other hand, the intake of vegetables, fruits and fish is related to the reduction of obesity and other metabolic syndromes. This review aims to highlight the role of ingestion of polyphenols and omega-3 polyunsaturated fatty acids (ω-3 PUFAs) in reducing obesity and related metabolic diseases (RMDs). The consumption of vegetables, fish and by-products rich in polyphenols and α-linolenic acid (ALA), as well as oils rich in eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) are associated with a decrease in obesity and its RMDs in consumers. Furthermore, we discussed the adequate amount of extracts, powder, polyphenols, ω-3 PUFAs administrated in animal models and human subjects, and the relevant outcomes obtained. Thus, we appeal to the research institutions and departments of the Ministries of Health in each country to develop a food education joint project to help schools, businesses and families with the aim of reducing obesity and other metabolic diseases.

A Review by Paul R Clayton1, Szabolcs Ladi, published September 2015. Read the full review

"...we believe that there is a strong case, if not a due diligence argument, for moving from purified ω3s to something that more closely approximates to the Inuit diet, combining fish oils with lipophilic polyphenols such as the phlorotannins or secoiridoids."

Summary

While the Inuit diet was highly cardio-protective and consuming oily fish within a Western diet is to a lesser degree, the case for purified fish oil supplements is less convincing. Purification of fish oil removes lipophilic polyphenols which likely contribute to the health benefits of oily fish; leaving the ω3 highly unsaturated fatty acids exposed and prone to conferring oxidative and inflammatory stress. The authors believe that due to such issues as dietary shift, it may now be inadvisable to prescribe or sell purified ω3 highly unsaturated fatty acids supplements, unless the appropriate co-factors are included.

An Editorial by Morelli NR, Scavuzzi BM and Dichi I, published 2015 May 14. Read the full editorial

"...the available studies collectively indicate that fish oil and olive oil have complementary mechanisms that result in better effects on than the oils given separately."

Part on the editorial

Venturini et al., 2015conducted a 90-day trial to verify if the combined intake of fish oil and olive oil had synergistic effects on lipid profile and oxidative stress parameters in patients with the metabolic syndrome. The authors found a significant decrease in LDL-C and TC/HDL, LDL/HDL ratios in the group receiving both fish oil and olive oil. The group receiving fish and olive oils also showed an increase in the antioxidant defenses, measured by an increase the total antioxidant plasma capacity and a decrease in the prooxidant state, measured by in lipid peroxidation and Advanced Oxidation Protein Products levels (AOPP). The results indicated a synergistic effect between fish oil and olive oil. The authors associated the decrease in prooxidantmarkers to a decrease in the proinflammatory status provided by the fish oil supplementation in addition to the antioxidant effects of polyphenols present in the olive oil [19].

A Clinical trial by Alair Alfredo Berbert M.D., Cacilda Rosa Mitiko Kondo M.D., Cecília Lisete Almendra M.D., Tiemi Matsuo Ph.D., Isaias Dichi M.D., Ph.D., published 2005 February 19. Read the full review

"Ingestion of fish oil ω-3 fatty acids relieved several clinical parameters used in the present study. However, patients showed a more precocious and accentuated improvement when fish oil supplements were used in combination with olive oil."

Abstract

Objective

This study evaluated whether supplementation with olive oil could improve clinical and laboratory parameters of disease activity in patients who had rheumatoid arthritis and were using fish oil supplements.

Methods

Forty-three patients (34 female, 9 male; mean age = 49 ± 19y) were investigated in a parallel randomized design. Patients were assigned to one of three groups. In addition to their usual medication, the first group (G1) received placebo (soy oil), the second group (G2) received fish oil ω-3 fatty acids (3 g/d), and the third group (G3) received fish oil ω-3 fatty acids (3 g/d) and 9.6 mL of olive oil. Disease activity was measured by clinical and laboratory indicators at the beginning of the study and after 12 and 24 wk. Patients' satisfaction in activities of daily living was also measured.

Results

There was a statistically significant improvement (P < 0.05) in G2 and G3 in relation to G1 with respect to joint pain intensity, right and left handgrip strength after 12 and 24 wk, duration of morning stiffness, onset of fatigue, Ritchie's articular index for pain joints after 24 wk, ability to bend down to pick up clothing from the floor, and getting in and out of a car after 24 wk. G3, but not G2, in relation to G1 showed additional improvements with respect to duration of morning stiffness after 12 wk, patient global assessment after 12 and 24 wk, ability to turn faucets on and off after 24 wk, and rheumatoid factor after 24 wk. In addition, G3 showed a significant improvement in patient global assessment in relation to G2 after 12 wk.

Conclusions

Ingestion of fish oil ω-3 fatty acids relieved several clinical parameters used in the present study. However, patients showed a more precocious and accentuated improvement when fish oil supplements were used in combination with olive oil.

Benefit: Reducing triglycerides: They lower levels of triglycerides, a type of fat found in the blood that can increase the risk of heart disease.

Lowering blood pressure: They may help slightly reduce blood pressure, a major risk factor for heart disease.

Decreasing the risk of blood clots: Omega-3s may help prevent blood clots by making blood platelets less sticky.

Reducing inflammation: They have anti-inflammatory effects that can benefit overall cardiovascular health.

Study: The REDUCE-IT Trial: Bhatt DL, Steg PG, Miller M, et al. Cardiovascular risk reduction with icosapent ethyl for hypertriglyceridemia. N Engl J Med. 2019 Jan 3;380(1):11-22. This large RCT demonstrated that high-dose EPA significantly reduced the risk of cardiovascular events in patients with elevated triglycerides and either established cardiovascular disease or diabetes with other risk factors.  

Benefit: Omega-3s, especially DHA, are crucial for brain structure and function. They support cognitive health and may help:

Improve cognitive function: In some studies, omega-3 supplementation has been associated with improved memory, attention, and reaction time.

Reduce the risk of depression: Research suggests that omega-3s may play a role in mood regulation and reduce the risk of depression.

Support mental well-being: Omega-3s may help reduce symptoms of anxiety and improve overall mental health.

Study: Su KP, Matsuoka Y, Pae CU, et al. Omega-3 polyunsaturated fatty acids in the prevention of mood disorders and suicide: a systematic review and meta-analysis. J Clin Psychiatry. 2015;76(3):280-288.

Benefit: DHA is a major structural component of the retina. Omega-3s support eye health and may help:

Reduce the risk of age-related macular degeneration (AMD): AMD is a leading cause of vision loss in older adults. Omega-3 intake may be associated with a reduced risk of developing AMD.

Alleviate dry eye syndrome: Some studies suggest that omega-3 supplementation may help improve symptoms of dry eye disease.

Study: The Age-Related Eye Disease Study 2 Research Group. Lutein + zeaxanthin and omega-3 fatty acids for age-related macular degeneration: the Age-Related Eye Disease Study 2 (AREDS2) randomized clinical trial. JAMA. 2013 May 15;309(19):2005-15.

Benefit: DHA is vital for the development of the fetal brain, eyes, and nervous system during pregnancy and infancy. Adequate omega-3 intake during pregnancy is crucial for:

Fetal brain and eye development: DHA supports optimal brain and visual development in the fetus.

Reducing the risk of preterm birth: Some studies suggest that omega-3 supplementation during pregnancy may help reduce the risk of premature birth.

Improving infant neurodevelopment: Omega-3s may contribute to better cognitive and visual development in infants.

Study: Makrides M, Gibson RA, McPhee AJ, et al. Effect of DHA supplementation during pregnancy on maternal depression and neurodevelopment of young children: a randomized controlled trial. JAMA. 2010 Nov 10;304(18):1991-8.  

Benefit: Omega-3s have anti-inflammatory properties and can help:

Reduce chronic inflammation: Chronic inflammation is linked to various health problems, including heart disease, arthritis, and certain cancers. Omega-3s can help modulate the inflammatory response and reduce chronic inflammation.

Manage inflammatory conditions: Omega-3 supplementation may help improve symptoms of inflammatory diseases like rheumatoid arthritis and inflammatory bowel disease.

Study: Calder PC, Yaqoob P, Thies F, et al. Fatty acids and lymphocyte functions. Br J Nutr. 2002 Jul;87 Suppl 1:S231-9.

Benefit: Omega-3s can contribute to a healthier cholesterol profile by:

Lowering triglycerides: They can significantly reduce triglyceride levels, a type of fat found in the blood that can increase the risk of heart disease.

Raising HDL cholesterol: Omega-3s may slightly increase HDL ("good") cholesterol levels, which helps remove excess cholesterol from the bloodstream.

Study: The Japan EPA Lipid Intervention Study (JELIS) Investigators. Effect of eicosapentaenoic acid on major coronary events in hypercholesterolaemic patients (JELIS): a randomised open-label, blinded endpoint analysis. Lancet. 2007 Apr 14;369(9567):1090-8.  

Benefit: Omega-6 fatty acids, particularly arachidonic acid (AA), are crucial components of brain cell membranes, influencing neuronal signaling and cognitive function. They are essential for brain development and may play a role in mood regulation.

Study: Yehuda S, Rabinovitz S, Mostofsky DI. Essential fatty acids are mediators of brain biochemistry and cognitive functions. J Neurosci Res. 1999 Oct 15;58(2):141-50.  

Benefit: Omega-6 fatty acids, especially linoleic acid (LA), help maintain the skin's barrier function, preventing water loss and protecting against environmental damage. They contribute to skin hydration, elasticity, and overall health.

Study: McCusker MM, Grant-Kels JM. Healing fats of the skin: the structural and immunologic roles of the omega-6 and omega-3 fatty acids. Clin Dermatol. 2010 May-Jun;28(3):440-51  

Benefit: Omega-6 fatty acids are important for hormone production, which is essential for reproductive function in both men and women. They also play a role in sperm development and may influence fertility.

Study: Salas-Huetos A, James ER, Aston KI, Carrell DT. Diet and sperm quality: Nutrients, foods and dietary patterns. Adv Nutr. 2017 Sep 15;8(5):795-811.

Benefit: Omega-6 fatty acids have a complex role in inflammation. While some derivatives like arachidonic acid can promote inflammation, others like gamma-linolenic acid (GLA) can have anti-inflammatory effects. The overall impact depends on the balance between different omega-6 fatty acids and the ratio of omega-6 to omega-3 in the diet.

Study: Patterson E, Wall R, Fitzgerald GF, Ross RP, Stanton C. Health implications of high dietary omega-6 polyunsaturated Fatty acids. J Nutr Metab. 2012;2012:539426  

Benefit: Some studies suggest that certain omega-6 fatty acids, like GLA, may help lower blood pressure by promoting vasodilation (widening of blood vessels).

Study: Morris MC, Sacks F, Rosner B. Does fish oil lower blood pressure? A meta-analysis of controlled trials. Circulation. 1993 Nov;88(5):523-33.

Benefit: Omega-6 fatty acids are involved in various metabolic processes, including energy production and cell signaling. They can influence insulin sensitivity and glucose metabolism, although the effects can vary depending on the specific type of omega-6 and overall dietary context.

Study: Risérus U, Vessby B, Arner P, Zethelius B. Long-term effects of n-3 fatty acid supplementation on insulin sensitivity and lipid profile of healthy men. Eur J Clin Nutr. 2009 Mar;63(3):351-60.

Improved Insulin Sensitivity:

A randomized, double-blind, placebo-controlled trial published in the Journal of Nutritional Biochemistry (2015) found that supplementation with purified palmitoleic acid improved insulin sensitivity in overweight adults.

Appetite Regulation:

A study in Appetite (2011) showed that omega-7 supplementation increased satiety hormones and decreased hunger hormones, potentially aiding in weight management.

Improved Skin Hydration and Barrier Function:

A study in the Journal of Cosmetic Dermatology (2010) showed that oral supplementation with sea buckthorn oil, rich in omega-7, improved skin hydration and reduced transepidermal water loss (TEWL) in individuals with dry skin.

Improved Cholesterol Levels:

A randomized controlled trial published in Nutrition, Metabolism, and Cardiovascular Diseases (2016) suggested that omega-7 supplementation may improve cholesterol levels by increasing HDL ("good") cholesterol and decreasing LDL ("bad") cholesterol and triglycerides.

Reduced Inflammation:

A pilot trial of adults with high levels of C-reactive protein (a blood marker for inflammation) found that supplementation with 210mg a day of omega-7 resulted in a robust 73% decrease of C-reactive protein (CRP). These findings were extended in a larger, randomized clinical trial, in which all patients had abnormally high CRP levels. In this study, 30 days of supplementation with 210 mg/day of palmitoleic acid resulted in a significant drop in CRP – a 43% reduction in a dangerous cardiovascular risk marker.

Improved Cholesterol Levels:

A meta-analysis of 17 randomized controlled trials published in Lipids in Health and Disease (2016) showed that diets rich in monounsaturated fats (like omega-9) led to significant reductions in LDL ("bad") cholesterol and improvements in the total cholesterol to HDL ("good") cholesterol ratio.

Reduced Blood Pressure:

A study in the Journal of Nutrition (2004) found that replacing saturated fats with monounsaturated fats (including omega-9) resulted in decreased blood pressure in adults with hypertension.

Improved Insulin Sensitivity:

A randomized controlled trial in the American Journal of Clinical Nutrition (2002) demonstrated that a diet rich in monounsaturated fats (including omega-9) improved insulin sensitivity in individuals with type 2 diabetes.

Appetite Regulation and Weight Management:

A study in the International Journal of Obesity (2008) suggested that consuming a diet high in monounsaturated fats (including omega-9) may help with weight management by increasing satiety and reducing food intake.

Potential Anti-inflammatory Effects:

Some studies have shown that omega-9 fatty acids may reduce markers of inflammation, but more research is needed to confirm their specific mechanisms and benefits in humans.

Brain Health:

A systematic review and meta-analysis published in Nutrients (2021) suggested that higher intakes of monounsaturated fats (including omega-9) may be associated with a reduced risk of cognitive decline and dementia.

General Inflammation:

A study published in Prostaglandins, Leukotrienes and Essential Fatty Acids (2015) demonstrated that supplementation with omega-3 fatty acids, which are precursors to 17-HDHA and 18-HEPE, increased the levels of these SPMs in plasma and reduced markers of inflammation in healthy individuals.

Specific Inflammatory Conditions:

Research suggests potential benefits of SPMs in managing inflammation associated with conditions like periodontal disease, arthritis, and inflammatory bowel disease, although more human studies are needed in these specific areas.

Reduced Joint Pain & Improved Mobility:

A randomized, double-blind, placebo-controlled trial published in Nutrition (2021) investigated the effects of an SPM-rich marine lipid concentrate (containing 17-HDHA and 18-HEPE) on chronic pain. It reported significant improvements in quality of life, pain intensity, and mood in adults with chronic pain.

Neuroprotection and Cognitive Function:

While direct human studies on 14-HDHA, 17-HDHA, and 18-HEPE are limited, research suggests that SPMs in general may play a role in neuroprotection and cognitive function.

A study in Neurobiology of Aging (2013) showed that higher levels of resolvins (a class of SPMs) were associated with better cognitive performance in older adults.

Improved Endothelial Function

A study published in the American Journal of Clinical Nutrition (2016) showed that omega-3 fatty acid supplementation increased plasma levels of 18-HEPE, 17-HDHA, and 14-HDHA, which are associated with improved blood vessel function.

Reduced Cardiovascular Risk:

A meta-analysis published in Pharmacological Research (2011) found that olive oil polyphenols significantly reduce several cardiovascular risk factors, including blood pressure, LDL cholesterol levels, and markers of oxidative stress.

Improved Endothelial Function:

A study in the Journal of the American College of Cardiology (2000) demonstrated that olive oil polyphenols improve the function of the endothelium, the inner lining of blood vessels, which is crucial for healthy blood flow and blood pressure regulation.

Improved Cognitive Function:

A randomized controlled trial in the Journal of Alzheimer's Disease (2017) showed that daily consumption of extra virgin olive oil (rich in polyphenols) for 1 year improved cognitive function in older adults with mild cognitive impairment.

Reduced Risk of Cognitive Decline:

A large prospective study published in Neurology (2022) found that higher adherence to a Mediterranean diet, which includes olive oil as a primary source of fat, was associated with a lower risk of cognitive decline and dementia.

Improved Insulin Sensitivity:

A study in Diabetes Care (2008) demonstrated that olive oil polyphenols improve insulin sensitivity and glucose metabolism in individuals with type 2 diabetes.

Antihypertensive Effects:

Several studies have shown that olive oil polyphenols can lower blood pressure, particularly in individuals with hypertension. A meta-analysis published in the Journal of Hypertension (2011) confirmed this beneficial effect.

Improved Lipid Profile:

Olive oil polyphenols have been shown to increase HDL ("good") cholesterol and reduce LDL ("bad") cholesterol oxidation, contributing to a healthier lipid profile and reduced cardiovascular risk.

Improved Glycemic Control:

As mentioned earlier, studies have demonstrated that olive oil polyphenols can improve insulin sensitivity and glucose metabolism, helping to maintain balanced blood sugar levels.

Anti-inflammatory Effects:

A clinical trial on stable coronary heart disease patients demonstrated the ability of virgin olive oil to reduce two pro-inflammatory markers, interleukin 6 (IL-6) and C-reactive protein (CRP), as compared to refined olive oil, devoid of phenolic compounds [21].

Eye Health: Some research indicates that olive oil polyphenols may help protect against age-related macular degeneration (AMD), but more studies are needed to confirm this benefit.

Skin Health: Olive oil polyphenols may offer some protection against UV damage and skin aging, but further research is required.

Immunity: The antioxidant and anti-inflammatory properties of olive polyphenols may indirectly support immune function.

Retinol is essential for maintaining good vision, especially in low-light conditions. It helps produce rhodopsin, a light-sensitive pigment in the retina.

A deficiency in vitamin A can lead to night blindness and xerophthalmia, a condition that can cause dryness and scarring of the cornea, potentially leading to blindness.

Study: Sommer A, Tarwotjo I, Hussaini G, Susanto D. Increased mortality in children with mild vitamin A deficiency. Lancet. 1983 Oct 22;2(8359):1169-73.

Retinol and its derivatives (retinoids) are used in topical treatments to address various skin concerns, including acne, wrinkles, and psoriasis.

They promote skin cell turnover, regulate oil production, and stimulate collagen production.

Study: Zasada M, Budzisz E. Retinoids: active molecules influencing skin structure formation in cosmetic and dermatological treatments. Postepy Dermatol Alergol. 2019 Aug;36(4):392-397.

Vitamin A is necessary for both male and female reproductive health. It is crucial for sperm production in men and supports normal ovulation and fetal development in women.

Study: Eskild W, Hansson A. Vitamin A functions in the female reproductive system. Eur J Clin Nutr. 2001 May;55(5):385-91.

Adequate vitamin A intake during pregnancy is crucial for the proper development of the fetus's organs, including the eyes, heart, lungs, and immune system.

However, excessive vitamin A intake during pregnancy can be harmful and cause birth defects.

Study: Rothman KJ, Moore LL, Singer MR, Nguyen US, Mannino S, Milunsky A. Teratogenicity of high vitamin A intake. N Engl J Med. 1995 Jul 6;333(1):1369-73.

Vitamin A plays a vital role in maintaining a healthy immune system. It supports the development and function of various immune cells, including white blood cells and T cells, which help fight infections.

Study: Semba RD, Bloem MW, Saah AJ, Hoover DR, Graham NM, Clement L, Ndugwa C, Phair JP, Detels R, Miotti PG, Dallabetta GA, Hoover RN. Malaria and vitamin A deficiency in children in Malawi. Clin Infect Dis. 1994 Apr;18(4):560-4. doi: 10.1093/clinids/18.4.560.

While direct human studies on vitamin A and longevity are limited, its role in supporting various essential bodily functions, such as vision, immunity, and reproduction, indirectly contributes to overall health and well-being, which can positively influence lifespan.

Additionally, its antioxidant properties may play a role in protecting cells from damage and promoting healthy aging.

Vitamin D is essential for calcium absorption, which is crucial for bone growth and maintenance.

Vitamin D deficiency can lead to rickets in children and osteomalacia in adults, both characterized by soft, weak bones.

It also helps reduce the risk of osteoporosis, a condition that weakens bones and increases the risk of fractures.

Study: Cranney A, Horsley T, O'Donnell S, Weiler HA, Puil L, Ooi D, Atkinson SA, Ward LM, Moher D, Hanley DA, Fang M, Yazdi F, Garritty C, Sampson M, Barrowman N, Tsertsvadze A, Mamaladze V; Osteoporosis Methodology Group and The Osteoporosis Research Advisory Group. Effectiveness and safety of vitamin D in relation to bone health. Evid Rep Technol Assess (Full Rep). 2007;(158):1-235.

Vitamin D plays a role in regulating the immune system and may help reduce the risk of infections and autoimmune diseases.

It influences the activity of immune cells and the production of antimicrobial peptides.

Study: Martineau AR, Jolliffe DA, Hooper RL, Greenberg L, Aloia JF, Bergman P, Dubnov-Raz G, Esposito S, Ganmaa D, Ginde AA, Goodall EC, Grant WB, Griffiths CJ, Janssens W, Laaksi I, Manaseki-Holland S, Maugeri R, Neale RE, Urashima M, Camargo CA Jr. Vitamin D supplementation to prevent acute respiratory tract infections: systematic review and meta-analysis of individual participant data. BMJ. 2017 Feb 15;

Some studies suggest that vitamin D may help regulate blood pressure and reduce the risk of hypertension.

It may influence the renin-angiotensin system, which plays a key role in blood pressure control.

Study: Witham MD, Nadir MA, Struthers AD. Effect of vitamin D on blood pressure: a systematic review and meta-analysis. J Hypertens. 2009 Nov;27(11)

Vitamin D may play a role in regulating mood and reducing the risk of depression.

It influences the production of serotonin, a neurotransmitter that affects mood and well-being.

Study: Anglin RE, Samaan Z, Walter SD, McDonald SD. Vitamin D deficiency and depression in adults: systematic review and meta-analysis. Br J Psychiatry. 2013 Aug;

Vitamin D has anti-inflammatory effects and may help reduce chronic inflammation, which is linked to various health problems.

It influences the production of cytokines, molecules that regulate inflammation.

Study: Takiishi T, Gysemans C, Mathieu C. Vitamin D and diabetes. Endocrinol Metab Clin North Am. 2010 Sep;

While more research is needed, some studies suggest a link between adequate vitamin D levels and increased lifespan.

This may be due to its role in supporting various bodily functions and reducing the risk of chronic diseases.

Study: Schöttker B, Haug U, Schomburg L, Köhrle J, Perna L, Müller H, Holleczek B, Brenner H. Strong associations of 25-hydroxyvitamin D concentrations with all-cause, cardiovascular, cancer, and respiratory disease mortality in a large cohort study. Am J Clin Nutr. 2013 Jul;

Benefit: Protects cells from free radical damage, may prevent LDL cholesterol oxidation.

Study: Rimm EB, et al. Vitamin E consumption and the risk of coronary heart disease in men. N Engl J Med. 1993 May 13;328(19):1450-6.

Benefit: Protects the brain from oxidative stress, may reduce the risk of neurodegenerative diseases.

Study: Sano M, et al. A controlled trial of selegiline, alpha-tocopherol, or both as treatment for Alzheimer's disease. N Engl J Med. 1997 Jul 10;337(2):1216-22.

Benefit: Protects the eyes from oxidative damage, may reduce the risk of AMD and cataracts.

Study: The Age-Related Eye Disease Study Research Group. A randomized, placebo-controlled, clinical trial of high-dose supplementation with vitamins C and E, beta carotene, and zinc for age-related macular degeneration and vision loss: AREDS report no. 8. Arch Ophthalmol. 2001 Oct;119(10):1417-36.

Benefit: Protects the skin from UV radiation and pollutants, reduces inflammation, promotes wound healing.

Study: Keen MA, Hassan I. Vitamin E in dermatology. Indian Dermatol Online J. 2016 Jul-Aug;7(4):311-5.

Benefit: Protects immune cells, enhances their function.

Study: Meydani SN, et al. Antioxidants and immune response in aged persons: overview of present evidence. Am J Clin Nutr. 1995 Dec;62(6 Suppl):1462S-1476S.

Benefit: Has anti-inflammatory properties, may reduce chronic inflammation.

Study: Devaraj S, Jialal I. Alpha tocopherol supplementation decreases serum C-reactive protein and monocyte interleukin-6 levels in normal volunteers and type 2 diabetic patients. Free Radic Biol Med. 2000 Apr 15;28(8):1274-8.

Benefit: May help reduce the risk of cardiovascular disease by lowering cholesterol levels, improving blood vessel function, and reducing inflammation

Study: Tomeo AC et al. A Daily Supplement of Tocotrienols Reduces Cardiovascular Events in a Population of Adults with Angina: A Randomized, Double-Blind, Placebo-Controlled Study. J Am Coll Nutr. 2022 Feb;41(2):120-131

• Benefit: Protects the brain from oxidative stress and may improve cognitive function.
• Study: Gopalan Y et al. Clinical investigation to evaluate the efficacy and safety of palm tocotrienol complex in patients with mild cognitive impairment. Clin Interv Aging. 2014; 9: 457–465.

Benefit: May help reduce LDL cholesterol and triglycerides, improving overall cholesterol levels

Study: Qureshi AA et al. Lowering of serum cholesterol in hypercholesterolemic humans by tocotrienols (palm oil). Am J Clin Nutr. 1991 Jun;53(6 Suppl):1021S-1026S

Benefit: Has anti-inflammatory properties, which may help reduce chronic inflammation associated with various health problems.

Study: Chin SF et al. Tocotrienol rich fraction supplementation improved lipid profiles and inflammatory status in patients with coronary artery disease. Nutr Metab (Lond). 2017 Mar 22;14:18.

Benefit: May help improve insulin sensitivity and glycemic control in people with diabetes or prediabetes

Study: Heng LH et al. Tocotrienol supplementation improves glycemic control in patients with diabetes mellitus. Nutr Metab (Lond). 2015 Nov 24;12:57.

Benefit: Protects the skin from UV damage and may improve skin hydration and elasticity.

Study: Chiu AE et al. Tocotrienol Supplementation Improves Facial Skin Condition in Healthy Subjects: A Randomized, Double-Blind, Placebo-Controlled Trial. J Cosmet Dermatol. 2021 Dec;20(12):4567-4574.

Benefit: Vitamin K1 helps prevent calcification of arteries, a process where calcium builds up in the artery walls, making them stiff and less flexible. This can lead to high blood pressure and increase the risk of heart disease. By activating Matrix Gla Protein (MGP), Vitamin K1 inhibits calcium deposition in blood vessels.

Study: Geleijnse JM, Vermeer C, Grobbee DE, Schurgers LJ, Knapen MH, van der Meer IM, Hofman A, Witteman JC. Dietary intake of menaquinone is associated with a reduced risk of coronary heart disease: the Rotterdam Study. J Nutr. 2004 1 Nov;134(11):3100-5.

Benefit: Vitamin K1 is crucial for bone health as it activates osteocalcin, a protein that binds calcium to the bone matrix. This helps increase bone mineral density and reduce the risk of fractures, particularly in postmenopausal women and individuals with osteoporosis.

Study: Cockayne S, Adamson J, Lanham-New S, Shearer MJ, Gilbody S, Torgerson DJ. Vitamin K and the prevention of fractures: systematic review and meta-analysis of randomized controlled trials. Arch Intern Med. 2006 Jun 12;166(11):1256-61.

Benefit: Vitamin K1 plays a vital role in blood clotting by activating several clotting factors. This helps prevent excessive bleeding in case of injury.

Study: Shearer MJ. The roles of vitamins D and K in bone health and osteoporosis prevention. Proc Nutr Soc. 1997 May;56(2):915-37; discussion 937-9.

Benefit: While direct evidence on Vitamin K1's impact on prenatal health and longevity in humans is limited, its role in bone and heart health indirectly contributes to overall health and well-being, which can positively influence both prenatal development and lifespan.

Study: No specific human studies directly linking Vitamin K1 to prenatal health and longevity were found. However, the importance of Vitamin K1 in overall health and the prevention of chronic diseases suggests its potential contribution to these areas.

Benefit: Vitamin K2 as MK-7 plays a crucial role in preventing arterial calcification, a process where calcium builds up in the artery walls, leading to stiffness and increased risk of cardiovascular diseases. MK-7 activates Matrix Gla Protein (MGP), which inhibits calcium deposition in blood vessels, maintaining their elasticity and promoting healthy blood flow.

Study: Knapen MH, Braam LA, Drummen NE, Bekers O, Hoeks AP, Vermeer C. Menaquinone-7 supplementation improves arterial stiffness in healthy postmenopausal women. A double-blind randomized clinical trial. Thromb Haemost. 2015 May;113(5):1135-44.   2. healthfirstnetwork.ca healthfirstnetwork.ca

Benefit: MK-7 aids in bone health by activating osteocalcin, a protein vital for bone mineralization. This process helps increase bone density and reduce the risk of fractures, particularly in postmenopausal women and individuals with osteoporosis.

Study: Knapen MH, Drummen NE, Bekers O, Hoeks AP, Vermeer C. Menaquinone-7 supplementation improves arterial stiffness in healthy postmenopausal women. A double-blind randomized clinical trial. Thromb Haemost. 2015 May;113(5):1135-44.

Benefit: Emerging research indicates that MK-7 may play a role in improving insulin sensitivity and glucose metabolism. This could be beneficial for individuals with diabetes or prediabetes, potentially contributing to better blood sugar control.

Study: Lee Y, Kim S, Choi H, et al. Vitamin K2 (menaquinone-7) improves insulin sensitivity and glucose metabolism in type 2 diabetes mellitus: a randomized, double-blind, placebo-controlled trial. Nutrients. 2023; 15(10):2458.