MULTIVITAMINS

There is a good case for the daily use of a multivitamin, as a nutrition insurance policy that helps to fill in the gaps for those nutrients people may not be getting in their diet. Furthermore, in a study¹ of 90,771 men and women, the regular use of a multivitamin was found to significantly improve adequate intake of nutrients compared to non-users. Also, research² found that multivitamin supplements are generally well tolerated, do not increase the risk of mortality, cerebrovascular disease, or heart failure, and their use likely outweighs any risk in the general population (and may be particularly beneficial for older people). So, the bottom line is that multivitamins really do work as a nutrition insurance policy.

Other multivitamin benefits
In addition to functioning as a nutrition insurance policy, the daily use of a multivitamin may offer other benefits as well.

Cardiovascular Disease
A 12-week, randomized, placebo-controlled study³ of 182 men and women (24 to 79 years) found that a multivitamin was able to lower homocysteine levels and the oxidation of LDLcholesterol—both of which are highly beneficial in reducing the risk for cardiovascular disease. Other multivitamin research⁴ has also demonstrated effectiveness in lowering homocysteine levels.

A 6-month, randomized, double-blind, placebo-controlled study⁵ of 87 men and women (30 to 70 years) found that multivitamin use was associated with lower levels of C-reactive protein, a measurement of inflammation associated with cardiovascular disease and other degenerative diseases. Other multivitamin research⁶ in women has shown similar results.

A Swedish, population-based, case-control study⁷ of 1296 men and women (45 to 70 years) who previously had a heart attack and 1685 healthy men and women as controls, found those using a multivitamin were less likely to have a heart attack. Other multivitamin research⁸ in Swedish women has shown similar results.

Cancer:
A large-scale, randomized, double-blind, placebo-controlled study⁹ was conducted with 14,641 male U.S. physicians initially 50 years or older, including 1312 men with a history of cancer, to determine the long-term effects of multivitamin supplementation on the incidence of various types of cancers. Results showed that during a median follow-up of 11.2 years, men with a history of cancer who took a daily multivitamin had a statistically significant reduction in the incidence of total cancer compared to those taking a placebo.

Stress/Energy:
A human clinical study¹⁰ with 96 healthy men (18 to 46 years) examined the effect of multivitamin supplementation in relation to plasma interleukin-6 (IL-6, a pro-inflammatory chemical produced by the body) and anger, hostility, and severity of depressive symptoms. The results showed that plasma IL-6 was associated with anger, hostility, and severity of depressive symptoms, and that multivitamin use was associated with lower plasma IL-6 levels.

A review¹¹ of the scientific literature indicated that patients complaining of fatigue, tiredness, and low energy levels may have low levels of vitamins and minerals. Certain risk groups like the elderly and pregnant women were identified, as was the role of B-vitamins in energy metabolism. Results found that supplementation with nutrients including B-vitamins (e.g., a multivitamin) can alleviate deficiencies, but supplements must be taken for an adequate period of time.

A meta-analysis¹² of eight randomized and placebo-controlled studies evaluated the influence of diet supplementation on stress and mood. Results showed that supplementation reduced the levels of perceived stress, mild psychiatric symptoms, anxiety, fatigue, and confusion. Supplements containing high doses of B-vitamins (e.g., multivitamins) may be more effective in improving mood states.

Aging:
At the ends of our chromosomes are stretches of DNA called telomeres. These telomeres protect our genetic data, making it possible for cells to divide. Each time a cell divides, telomeres get shorter. When they get too short, the cell can no longer divide and becomes inactive or “senescent” or dies. This process is associated with aging. In a cross-sectional analysis of data from 586 women (35 to 74 years), multivitamin use was assessed, and relative telomere length was measured. The results were that multivitamin use was significantly associated with longer telomeres. Compared with nonusers, the relative telomere length was on average 5.1 percent longer among daily multivitamin users. It is possible, therefore, that multivitamins may help us live longer.

VITAMIN D

Vitamin D is the “sunshine vitamin,” so coined because exposure to the sun’s ultraviolet light will convert a form of cholesterol under the skin into vitamin D. This nutrient is best known for its role in helping to facilitate the absorption of calcium and phosphorus (as well as magnesium), and so helping to promote bone health.¹³ Over the past decade, however, research on vitamin D has identified numerous other roles it plays in human health and wellness, which includes:

• Inhibiting the uncontrolled proliferation of cells (as in the case of cancer) and stimulating the differentiation of cells (specialization of cells for specific functions).¹⁴
• Helping prevent cancers of the prostate and colon.^15,16
• Functioning as a potent immune system modulator.^17,18
• Helping prevent autoimmune reactions.^19,20,21
• Helping improve insulin secretion.^22,23,24
• Decreasing the risk of high blood pressure via the reninangiotensin system’s regulation of blood pressure.²⁵
• Reducing osteoporotic fractures.^26,27,28
• Reducing the incidence of falls in older adults.^29,30
• Reducing the risk of developing premenstrual syndrome (PMS).³¹
• Reducing the prevalence of depression, especially in the elderly.³²
• Reducing the prevalence of urinary infections and lower urinary tract symptoms (e.g., benign prostatic hyperplasia or BPH).³³

Vitamin D deficiency and insufficiency
Outright vitamin D deficiency is present in 41.6 percent of the U.S. population,³⁴ while vitamin D insufficiency (i.e., lacking sufficient vitamin D) is present in 77 percent of the world’s population.³⁵ If you are deficient in vitamin D you will not be able to absorb enough calcium to satisfy your body’s calcium needs.³⁶ It has long been known that severe vitamin D deficiency has serious consequences for bone health, but other research indicates that lesser degrees of vitamin D deficiency are common and increase the risk of osteoporosis and other health problems.^37,38

Vitamin D sufficiency is measured by serum 25-hydroxyvitamin D levels in the body.³⁹ Laboratory reference ranges for serum 25-hydroxyvitamin D levels are based upon average values from healthy populations. However, recent research examining the prevention of secondary hyperparathyroidism and bone loss suggest that the range for healthy 25-hydroxyvitamin D levels should be considerably higher. Based upon the most current research, here are the ranges for serum 25-hydroxyvitamin D values:

• Less than 20–25 nmol/L: Indicates severe deficiency associated with rickets and osteomalacia.^40,41
• 50–80 nmol/L: Previously suggested as normal range.⁴²
• 75–125 nmol/L: More recent research suggests that parathyroid hormone^43,44 and calcium absorption⁴⁵ are optimized at this level; this is a healthy range.⁴⁶

Based upon the 75–125 nmol/L range, it is estimated that one billion people in the world are currently vitamin D deficient.⁴⁷ Furthermore, research indicates that supplementation with at least 800–1,000 IU daily are required to achieve serum 25-hydroxyvitamin D levels of at least 80 nmol/L.^48,49 Furthermore, there are many groups of individuals who currently are at risk for vitamin D deficiency. These include:

• Exclusively breast-fed infants: Especially if they do not receive vitamin D supplementation and if they have dark skin and/or receive little sun exposure.⁵⁰
• Dark skin: People with dark-colored skin synthesize less vitamin D from sunlight than those with light-colored skin.⁵¹ In a U.S. study, 42 percent of African American women were vitamin D deficient compared to four percent of white women.⁵²
• The Elderly: When exposed to sunlight have reduced capacity to synthesize vitamin D.⁵³
• Those using sunscreen: Applying sunscreen with an SPF factor of eight reduces production of vitamin D by 95 percent.⁵⁴
• Those with fat malabsorption syndromes: The absorption of dietary vitamin D is reduced in Cystic fibrosis and cholestatic liver disease.⁵⁵
• Those with inflammatory bowel disease: An increased risk of vitamin D deficiency occurs in those with inflammatory bowel disease like Crohn’s disease.⁵⁶
• Obese individuals: Obesity increases the risk of vitamin D deficiency.⁵⁷

Vitamin D2 and D3
There are two forms of vitamin D available as a dietary supplement: cholecalciferol (vitamin D3) and ergocalciferol (vitamin D2). Cholecalciferol is the form made in the human body, and it is more active than ergocalciferol. In fact, Vitamin D2 potency is less than one third that of vitamin D3.⁵⁸

Commercially, ergocalciferol is derived from yeast, and so is considered vegetarian, while cholecalciferol is commonly derived from lanolin (from sheep) or fish oil—although a vegetarian D3 derived from lichen is available.

Ideal dosing for vitamin D
The Linus Pauling Institute recommends that generally healthy adults take 2,000 IU of supplemental vitamin D daily.⁵⁹ The Vitamin D Council states that if well adults and adolescents regularly avoid sunlight exposure, then it is necessary to supplement with at least 5,000 IU of vitamin D daily.⁶⁰ The Council for Responsible Nutrition recommends 2,000 IU daily for adults.⁶¹ Taking a conservative position, at least 2,000 IU of vitamin makes sense for adults.

OMEGA-3 FATTY ACIDS
Chemically, a fatty acid is an organic acid that has an acid group at one end of its molecule, and a methyl group at the other end.⁶² Fatty acids are typically categorized in the omega groups 3, 6 and 9 according to the location of their first double bond (there’s also an omega 7 group, but these are less important to human health).⁶³ The body uses fatty acids for the formation of healthy cell membranes, the proper development and functioning of the brain and nervous system, and for the production of hormone-like substances called eicosanoids (thromboxanes, leukotrienes, and prostaglandins). These chemicals regulate numerous body functions including blood pressure, blood viscosity, vasoconstriction, immune and inflammatory responses.⁶⁴

Deficiency of omega-3 fatty acids
While omega-3, 6 and 9 fatty acids are all important for different reasons, it is the omega-3 fatty acids (O3FA) that are currently particularly critical—and specifically the O3FA known as eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA). The reason for this current importance is that Western diets are deficient in O3FA, and have excessive amounts of omega-6 fatty acids. While human beings evolved on a diet with approximately a 1:1 ratio of omega-6 to omega-3 fatty acids (EFA), the current Western diet provides about a 16:1 ratio.⁶⁵ As a matter of fact, a recent Harvard School of Public Health study indicates that Omega-3 deficiency causes 96,000 U.S. deaths per year.⁶⁶ Other research has clearly shown that excessive amounts of omega-6 fatty acids and a very high omega-6 to omega-3 ratio, as is found in today’s Western diets, promote many diseases, including cardiovascular disease, cancer, and inflammatory and autoimmune diseases, whereas increased levels of omega-3 (a low omega-6 to omega-3 ratio) exert protective effects.⁶⁷

Benefits of omega-3 fatty acids

O3FA offer a broad range of benefits in human health. These benefits are listed below categorically:

Cardiovascular Health
In several studies O3FA have been shown to help lower triglyceride levels.⁶⁸ In fact, the FDA has even approved an O3FA product for this purpose.⁶⁹ Individually, EPA and DHA also have triglyceride-lowering properties. Consuming 1 gram/day of fish oils from fish (about 3 ounces of fatty fish such as salmon) or fish oil supplements has a cardioprotective effect.⁷⁰

Evidence suggests increased consumption of O3FA from fish or fish-oil supplements, but not of alpha-linolenic acid, reduces the rates of all-cause mortality, cardiac and sudden death, and possibly stroke.⁷¹ Higher consumption of fish and O3FA has been associated with a lower risk of coronary heart disease.^72,73 Clinical research shows that DHA supplementation helps increase HDL cholesterol levels (the “good cholesterol”).^74,75 Supplementation with fish oil produces modest, but significant reductions in systolic and diastolic blood pressure in patients with mild hypertension.^76,77,78

Inflammation
O3FA have been shown to help relieve inflammation caused by a variety of factors.^79,80

Arthritis

Research⁸¹ has demonstrated that fish oil supplementation is effective in the treatment of rheumatoid arthritis.

Menopause
Clinical research shows that taking supplements with 500 mg EPA, three times daily, modestly but significantly reduces the frequency of hot flashes compared to placebo in menopausal women.⁸²

ADHD
Research has shown children with attention deficit/hyperactive disorder (ADHD) may have low plasma levels of EPA and DHA.^83,84 Clinical research suggests that supplementation with DHA might improve aggression and social relationships in ADHD children.⁸⁵

Macular degeneration
Increased dietary consumption of DHA is associated with reducing the risk of macular degeneration.⁸⁶

Alzheimer’s Disease
Participants who consumed fish once per week or more had 60 percent less risk of Alzheimer’s disease compared with those who rarely or never ate fish, and this was attributed to the DHA content of the fish.⁸⁷

The sources of omega-3 fatty acids

To begin with, the overwhelming majority of research on the health benefits of supplementation with O3FA has been conducted using fish oil products. Consequently, a strong argument can be made that fish oil supplements are the preferred source of O3FA. Amongst these, the primary fish used commercially as the source from which O3FA are derived include mackerel, herring, tuna, halibut, salmon and cod liver.⁸⁸ Although some fish are touted as superior over others as sources for supplemental fish oil, it is the opinion of this author that they all provide acceptable sources of omega-3s. Still, there are other sources of O3FA besides fish oil. This includes squid, krill, flax seed oil and algae oil.

Squid
Squid-derived O3FA are derived from by-products of squid that are usually discarded when squid are commercially fished, and provides a much higher concentration of DHA (up to 50 percent) than do fish oil. However, there is a lack of human clinical data on squid-source O3FA, although they likely will have similar effects as fish oil.

Krill
Krill oil derived from the shrimp-like crustacean know as krill contain significant amounts of the EPA and DHA omega-3 fatty acids, as well as phospholipids (e.g., phosphatidylcholine),⁸⁹ vitamin A, vitamin E and astaxanthin, a powerful carotenoid antioxidant.^90,91 Human clinical research⁹² has shown that krill oil has greater absorption than fish oil—although krill provides significantly less EPA/DHA per gram than fish oil.

Flaxseed
Flaxseed oil contains about 52–55 percent omega-3s, but as alpha-linolenic acid (ALA), not EPA/DHA.⁹³ This is significant since ALA has to be converted to EPA and DHA before it will provide the much-touted health benefits attributed to O3FA. This is problematic since studies indicate that in men approximately eight percent of ALA is converted to EPA and 0–4 percent is converted to DHA.⁹⁴ In women, approximately 21 percent of dietary ALA is converted to EPA and nine percent is converted to DHA.⁹⁵ This is not to say that flaxseed oil has no value. It does, but just not as significant a value as fish oil.

Algae oil
Certain algae extracts provide a vegetarian source of O3FA—but in this case the O3FA are EPA and DHA, not ALA. Consequently, for vegetarians, algae oil is a viable substitute for fish oil. That being said, human clinical research on algae oil sources of O3FA is limited, and the cost is far more than fish oil.

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85. Cho E, Hung S, Willet W, et al. Prospective study of dietary fat and the risk of age-related macular degeneration. Am J Clin Nutr. 2001;73:209–18.
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87. MedlinePlus. Fish Oil. U.S. National Library of Medicine. Last reviewed–12/10/2011.
88. Bottino NR. Lipid composition of two species of Antarctic krill: Euphausia superba and E. crystallorophias. Comp Biochem Physiol B 1975;50:479–84.
89. Ibid.
90. Dunlap WC, Fujisawa A, Yamamoto Y, et al. Notothenioid fish, krill and phytoplankton from Antarctica contain a vitamin E constituent (alphatocomonoenol) functionally associated with cold-water adaptation. Comp Biochem Physiol B Biochem Mol Biol 2002;133:299–305.
91. Ulven SM, Kirkhus B, Lamglait A, Basu S, Elind E, Haider T, Berge K, Vik H, Pedersen JI. Metabolic effects of krill oil are essentially similar to those of fish oil but at lower dose of EPA and DHA, in healthy volunteers. Lipids 2011;46(1):37–46.
92. Vereshagin AG and Novitskaya GV. The triglyceride composition of linseed oil. Journal of the American Oil Chemists’ Society 1965;42:970–4.
93. Burdge GC, Jones AE, Wootton SA. Eicosapentaenoic and docosapentaenoic acids are the principal products of alpha-linolenic acid metabolism in young men. Br J Nutr. 2002;88(4):355–64.
94. Burdge GC, Wootton SA. Conversion of alpha-linolenic acid to eicosapentaenoic, docosapentaenoic and docosahexaenoic acids in young women. Br J Nutr. 2002;88(4):411–20.

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About Inflammation

Let’s start with a brief review about inflammation, a useful natural reaction that the body has in response to injury and certain other conditions. Chronic inflammation, however, can be more destructive than beneficial and is a major component in many human diseases. Furthermore, it must be understood that chronic inflammation isn’t just associated with disease states. In fact, higher intakes of red and processed meats, sweets, desserts, French fries, and refined grains are associated with experiencing more inflammation,¹ as is exposure to colder temperatures (i.e. colder climates).²

Since prolonged inflammation is detrimental to the host, higher organisms have evolved protective mechanisms to ensure resolution of the inflammatory response in a limited and specific time-and space-manner. Once thought as a mere passive process of dilution of inflammation, resolution is today envisioned as a highly orchestrated process coordinated by a complex regulatory network of cells and mediators.³

Pro-resolving Mediators
Among the molecules that facilitate resolution of inflammation, resolvins, protectins, and maresins produced from O3FA are the lipid mediators which are particularly important. These internally produced anti-inflammatory and pro-resolving mediators counteract the effects of proinflammatory signaling systems and act as “braking signals” of the persistent vicious cycle leading to unremitting inflammation.

In fact, the same pro-inflammatory factors that initially trigger the inflammatory response also signal the termination of inflammation by stimulating the biosynthesis of pro-resolving mediators. Resolvins, protectins and maresins and have been shown to reduce airway inflammation, dermal inflammation colitis, arthritis, and postoperative pain. Studies have shown that these mediators increase with time during the inflammatory process.^4,5,6

DHA The most well-known O3FA are eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA). While these two O3FA can be used to generate resolvins, there is another O3FA called docosapentaenoic acid (DPA), which is a particularly effective precursor to different resolvins.⁷ DPA is an intermediate in the biosynthesis of DHA from EPA. In any case, DPA is not always seen in omega-3 fatty acid products. It can, however, be found in some cod liver oil products.

Cod Liver Oil And Inflammation

It should be noted that cod liver oil is a natural source of vitamins A and D, in addition to O3FA. This is significant since maintaining healthy vitamin D levels is necessary for supporting cardiovascular health,^8,9,10,11 and vitamin D plays an important role in healthy skin and in regulating a healthy immune system.¹² Furthermore, some cod liver oil products are a direct source of pro-resolving mediators. Not surprisingly, cod liver oil has shown value for its anti-inflammatory effects.

A study¹³ was conducted to compare the effects of supplementation with either sunflower oil (source of omega-6) or cod liver oil (source of omega-3) oil, in rates with inflammatory colitis. Inflammatory markers increased in rats fed sunflower oil but was blunted in rats fed cod liver oil. In fed cod liver oil group, the damage score was markedly reduced by day 30, and inflammation and ulceration were almost absent by day 50.

A 9-month, double-blind, placebo-controlled, randomized human study¹⁴ was conducted in 58 patients with rheumatoid arthritis (RA) to determine whether cod liver oil supplementation would help reduce daily NSAID (pain medication) requirement. Patients took either 10 g of cod liver oil containing or identical placebo capsules. Documentation of NSAID daily requirement, clinical and laboratory parameters of RA disease activity, and safety checks were done at 0, 4, 12, 24 and 36 weeks. At 12 weeks, patients were instructed to gradually reduce, and if possible, stop their NSAID intake. Results were that 39 percent of patients in the cod liver oil group and 10 percent of patients in the placebo group were able to reduce their daily NSAID requirement by more than 30 percent. Researchers concluded that cod liver oil supplements containing n-3 fatty acids can be used as NSAID-sparing agents in RA.

Cod Liver Oil and Beauty
In addition to inflammation, cod liver oil may also have a “beauty from within” application. Here’s the rationale. O3FA have been shown to help reduce the visible signs of aging, and support cell rejuvenation. In one study, a diet providing as little as 295 mg/day of EPA was shown to decrease the risk in photoaging (i.e. more rapidly aged skin due to sun exposure) in women.¹⁵ In addition, vitamin D has been shown to play an important role in maintaining healthy hair due to its relationship with vitamin D receptors in hair follicles.^16,17,18 Given that cod liver oil is a natural source of both O3FA and vitamin D, it may serve as an ideal supplement for the skin and hair.

Conclusion
Due to its naturally occurring EPA, DHA, DPA, and pro-resolving mediators, cod liver oil is an ideal supplement for helping to reduce inflammation. Furthermore, it is a natural source of vitamins A and D; and may also have “beauty from within” applications. That being said, if you’re going to use a cod liver oil supplement, it is important to use a clean product. I suggest looking for supplements from cod from Alaskan waters (a more pristine area) that are line-caught and flash-frozen to preserve freshness.

References:

1. Lopez-Garcia E, Schulze MB, Fung TT, Meigs JB, Rifai N, Manson JE, Hu FB. Major dietary patterns are related to plasma concentrations of markers of inflammation and endothelial dysfunction. Am J Clin Nutr. 2004 Oct;80(4):1029–35.
2. Halonen JI, Zanobetti A, Sparrow D, Vokonas PS, Schwartz J. Associations between outdoor temperature and markers of inflammation: a cohort study. Environ Health. 2010 Jul 23;9:42.
3. Clària J. Resolution of Acute Inflammation and the Role of Lipid Mediators. Scientific World Journal. 2010; 10:1553–5.
4. Recchiuti A, Serhan CN. Pro-resolving lipid mediators (SPMs) and their actions in regulating miRNA in novel resolution circuits in inflammation. Front Immunol. 2012 Oct 22;3:298.
5. Serhan CN. Novel Pro-Resolving Lipid Mediators in Inflammation Are Leads for Resolution Physiology. Nature. 2014 Jun 5; 510(7503): 92–101.
6. Spite M, Serhan CN. Novel lipid mediators promote resolution of acute inflammation: impact of aspirin and statins. Circ Res. 2010 November 12; 107(10): 1170–84.
7. Primdahl KG, Aursnes M, Walker ME, Colas RA, Serhan CN, Dalli J, Hansen TV, Vik A. Synthesis of 13(R)-Hydroxy- 7Z,10Z,13R,14E,16Z,19Z Docosapentaenoic Acid (13R-HDPA) and Its Biosynthetic Conversion to the 13-Series Resolvins. J Nat Prod. 2016 Oct 28;79(10):2693–2702.
8. Wang TJ, Pencina MJ, Booth SL, et al. Vitamin D deficiency and risk of cardiovascular disease. Circulation 2008;117;503–11.
9. Dobnig H, Pilz S, Scharnagl H, et al. Independent association of low serum 25-hydroxyvitamin D and 1,25-dihydroxyvitamin D levels with all-cause and cardiovascular mortality. Arch Intern Med 2008;168:1340–49.
10. Giovannucci E, Liu Y, Hollis BW, Rimm EB. 25-hydroxyvitamin D and risk of myocardial infarction in men. Arch Intern Med 2008;168:1174–80.
11. Martins D, Wolf M, Pan D, et al. Prevalence of cardiovascular risk factors and the serum levels of 25-hydroxyvitamin D in the United States. Arch Intern Med 2007;167:1159–65.
12. Institute of Medicine. Food and Nutrition Board. Vitamin A. Dietary Reference Intakes for Vitamin A, Vitamin K, Arsenic, Boron, Chromium, Copper, Iodine, Iron, Manganese, Molybdenum, Nickel, Silicon, Vanadium, and Zinc. National Academy Press, Washington, DC; 2001:82–161.
13. Vilaseca J, Salas A, Guarner F, Rodríguez R, Martínez M, Malagelada JR. Dietary fish oil reduces progression of chronic inflammatory lesions in a rat model of granulomatous colitis. Gut. 1990 May;31(5):539–44.
14. Galarraga B, Ho M, Youssef HM, Hill A, McMahon H, Hall C, Ogston S, Nuki G, Belch JJ. Cod liver oil (n-3 fatty acids) as an nonsteroidal anti-inflammatory drug-sparing agent in rheumatoid arthritis. Rheumatology (Oxford). 2008 May;47(5):665–9.
15. Latreille J, Kesse-Guyot E, Malvy D, Andreeva V, Galan P, Tschachler E, Hercberg S, Guinot C, Ezzedine K. Association between dietary intake of n-3 polyunsaturated fatty acids and severity of skin photoaging in a middle-aged Caucasian population. J Dermatol Sci. 2013 Dec;72(3):233–9.
16. Daroach M1, Narang T, Saikia UN, Sachdeva N, Sendhil Kumaran M. Correlation of vitamin D and vitamin D receptor expression in patients with alopecia areata: a clinical paradigm. Int J Dermatol. 2018 Feb;57(2):217–222.
17. Gerkowicz A, Chyl-Surdacka K, Krasowska D, Chodorowska G. The Role of Vitamin D in Non- Scarring Alopecia. Int J Mol Sci. 2017 Dec 7;18(12).
18. Cheung EJ, Sink JR, English Iii JC. Vitamin and Mineral Deficiencies in Patients With Telogen Effluvium: A Retrospective Cross-Sectional Study. J Drugs Dermatol. 2016 Oct 1;15(10):1235–37.

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Resveratrol Background
Before jumping into a discussion about the fascinating human research, however, let’s take a moment to review just what resveratrol is, in case you’re unfamiliar with it. Resveratrol is a type of natural phenol by several plants in response to injury or attack by pathogens.^3,4 These plants include grapes, peanuts⁵ and Japanese Knotweed (Polygonum cuspidatum).⁶ Resveratrol helps provide protection to the plants, at least in part, due to its demonstrated antioxidant properties.⁷ These antioxidant properties benefit humans too, as shown in research where resveratrol provided a direct antioxidant effect against free radicals, and facilitated an increase in vitamin E⁸—another powerful antioxidant.

There are two primary isomers (i.e. two forms) of resveratrol, trans- and cis-. To be clear, trans-resveratrol has been unequivocally shown to have much greater activity than cis-resveratrol.⁹ Consequently, when purchasing a resveratrol product, make sure to check the supplement facts panel to verify that the product contains trans-resveratrol. If just”resveratrol” is listed, without the trans-designation, or if cis-resveratrol is listed, you would be better off choosing a different product that lists trans-resveratrol. In any case, for ease of reading, I will drop references to trans– in the rest of this article, although it can be assumed that any mention of resveratrol will actually refer to trans-resveratrol.

Cardiovascular Health
As its first claim to fame, resveratrol has been found to have activity that may have protective effects on the cardiovascular system. In both test-tube and animal research, resveratrol has been shown to inhibit platelet aggregation (i.e. the clumping together of blood platelets). This has value since excessive or inappropriate aggregation of platelets can lead to formation of blood clots and subsequent blockages in blood vessels that result in insufficient blood flow, heart attack or stroke.¹⁰ Resveratrol can also promote vasodilation (a relaxed and expanded state of the artery that accommodates increased blood flow) by enhancing the production of a naturally occurring substance in the body called nitric oxide.¹¹

More importantly, human clinical research¹² has demonstrated that 100 mg/day of resveratrol significantly reduced arterial stiffness (a major indicator of atherosclerosis) compared to placebo, and also lowered systolic blood pressure by 5.5 points in patients with type 2 diabetes. Another human study,¹³ which used a much higher dose (2.3 g) in older adults, found that resveratrol not only improved vascular function more than placebo, but also increased the number of mitochondria.those parts of the cells that help to generate energy for our body! Another interesting cardiovascular benefit is resveratrol’s effect on Apolipoprotein B (ApoB), a primary component of many lipoproteins such as LDL (the gbad cholesterolh) that are involved in atherosclerosis and cardiovascular disease. In human clinical research¹⁴ on overweight or obese individuals with mild hypertriglyceridemia, 1000 mg/day of resveratrol for one week followed by 2000 mg/day for two weeks reduced ApoB production rate by an impressive 22 percent. In addition, flow-mediated dilatation (a measure of arterial circulation and endothelial function) was increased in human studies^15,16,17 where 10 mg to 270 mg/day of resveratrol was given. In one of the studies,¹⁸ LDL cholesterol levels were also significantly decreased.

Inflammation
In addition to showing anti-inflammatory effects in in-vitro and animal studies, resveratrol has also been shown to comprehensively suppress oxidative and inflammatory stress with as little as 40 mg/day in normal human subjects.¹⁹ This included the reduction of inflammatory markers such as TNF-alpha, IL-6, and C-reactive protein, with no changes in the placebo group. Similarly, in postmenopausal women with osteoarthritis pain, 75 mg of resveratrol twice daily significantly reduced pain and improved total well-being.²⁰

Ulcerative colitis (UC), a chronic inflammatory bowel disease, has also responded to treatment with resveratrol. In one study²¹ with 56 UC patients, those receiving 500 mg/day of resveratrol had significant symptom improvement, reduced malondialdehyde (a highly reactive oxidative stress compound), and increased superoxide dismutase (SOD), and total antioxidant capacity. In another human study²² with 50 UC patients, 500 mg/day of resveratrol also reduced the activity of inflammatory compounds, including TNF-α, hs-CRP, and activity of NF-κB. Furthermore, in a study²³ of firefighters, supplementation with 100 mg/day resveratrol for 90 days, plasma biomarkers of inflammation were reduced after a physical fitness test, including IL-6 and TNF-α. This adds further credence to resveratrol’s anti-inflammatory effects.

Immune Health/Breast Cancer Prevention
Resveratrol’s effect on immune health can be as fundamental as increasing certain circulating immune cells, or as profound at reducing the risk of breast cancer. For example, human research²⁴ was conducted to assess the effects of repeated doses of resveratrol (1000 mg/day for 28 days) on circulating immune cells in healthy individuals. The results were that resveratrol was safe and well tolerated and was associated with significant increases in the numbers of circulating gamma delta T cells (functioning as a first line of defense and a bridge between innate and adaptive responses) and regulatory T cells—demonstrating that resveratrol has clear biological effects on human circulating immune cells.

With regard to breast cancer prevention, resveratrol may help in a couple of ways. First, resveratrol has been shown to have a dose-dependent effect on reducing the formation of mammary tumors in-vitro as a result of down-regulating DNA methyltransferases. To see if it had a similar effect in humans, a study²⁵ was conducted in which 39 adult women at increased breast cancer risk received a placebo, 5 or 50 mg of resveratrol twice daily for 12 weeks. Results were that there was indeed decrease in methylation of the tumor suppressor gene with increasing levels of resveratrol (P = .047).

In another study²⁶ of 34 overweight, postmenopausal women (BMI ≥ 25 kg/m2), the clinical effect of resveratrol on systemic sex steroid hormones were investigated, since high estrogen levels may contribute to breast cancer. The subjects received 1 g of resveratrol daily for 12 weeks. The results were that resveratrol supplementation led to an average of 73 percent increase in urinary 2-hydroxyestrone (the “good estrogen”) levels leading to a favorable change in estrogen ratios that are less conducive to the development of breast cancer. This research demonstrated that among overweight and obese postmenopausal women, a daily 1 g dose of resveratrol has favorable effects on estrogen metabolism.

Muscle Health
In a 12-week study,²⁷ older men and women (aged 65.80 years) exercised and took either a placebo or 500 mg/day of resveratrol to determine if resveratrol would have additive effects to those of exercise. Results showed that exercise added to resveratrol treatment increased the number of mitochondria, and improved muscle fatigue resistance more than placebo and exercise treatments. In addition, subjects treated with resveratrol had an increase in muscular torque and power after training, whereas exercise did not increase these parameters in the placebo-treated older subjects. Furthermore, exercise combined with resveratrol significantly improved muscle fiber. Together, these data suggest that resveratrol combined with exercise might provide a better approach for reversing sarcopenia than exercise alone.

Cognitive Health
Research suggests that resveratrol may have cognitive health benefits in people with and without dementia. For example, the ongoing dysfunction of small blood vessels in patients with type 2 diabetes mellitus (T2DM) may impair the ability of cerebral vessels to supply blood to various brain regions, thereby increasing risks of dementia. To determine if resveratrol could benefit cerebral circulation, a study²⁸ was conducted in which 36 dementia-free, non-insulin dependent T2DM older adults (49–78 years old) consumed single doses of resveratrol (0, 75, 150, and 300 mg) at weekly intervals. Results were that 75–300 mg of resveratrol enhanced vasodilator responsiveness in cerebral vessels.

In another study,²⁹ 80 post-menopausal women aged 45–85 years received resveratrol or placebo for 14 weeks to examine the effect on cognitive performance and other parameters. Results were that compared to placebo, significant improvements were observed in the performance of cognitive tasks in the domain of verbal memory (p = 0.041) and in overall cognitive performance (p = 0.020). Mood also tended to improve in multiple measures. These results indicate that regular consumption of a modest dose of resveratrol can enhance both cerebrovascular function and cognition in post-menopausal women, potentially reducing their heightened risk of accelerated cognitive decline and offering a promising therapeutic treatment for menopause-related cognitive decline.

To test³⁰ whether supplementation of resveratrol (200 mg/ day for 26 weeks) would enhance memory performance in older adults, 23 healthy overweight older individuals were pairwise matched to 23 participants that received placebo (total n = 46, 18 females, 50–75 years). Results showed a significant effect of resveratrol on retention of words over 30 min compared with placebo (p = 0.038), significant increases in hippocampal functional connectivity, decreases in glycated hemoglobin (HbA1c) and body fat, and increases in leptin compared with placebo (all p < 0.05). This study provides initial evidence that supplementary resveratrol improves memory performance in association with improved glucose metabolism in older adults, providing a basis for helping to maintain brain health during aging.

To determine the effects of oral resveratrol on localized cerebral blood flow, a study³¹ was conducted with which 22 healthy human adults received placebo and two doses (250 and 500 mg) of resveratrol in counterbalanced order on separate days. After a 45-min resting absorption period, the participants performed a selection of cognitive tasks. Resveratrol administration resulted in dose-dependent increases in cerebral blood flow during task performance, and enhanced oxygen extraction. These results showed that single doses of orally administered resveratrol can modulate cerebral blood flow variables.

Finally, a clinical study³² was conducted to determine if up to 1 g of resveratrol twice daily could benefit Alzheimer’s disease (AD) patients. The results demonstrated that resveratrol decreased CSF MMP9 (a biomarker for confirmed AD), modulates neuro-inflammation, and induces adaptive immunity— suggesting that resveratrol may be a viable target for treatment or prevention of neurodegenerative disorders.

Weight Loss
One of the reasons that resveratrol has received widespread interest is because of its ability to mimic effects of calorie restriction. To gain more insight into this effect on adipose tissue, a study³³ was conducted in which healthy obese subjects were supplemented with 150 mg/day of resveratrol or placebo for 30 days. Results showed that resveratrol significantly decreased the size of adipocytes (fat cells), with a shift toward reducing the proportion of large and very-large adipocytes and an increase in small adipocytes. Furthermore, lysosomal/phagosomal pathway and transcription factor EB were up-regulated reflecting an alternative pathway of lipid breakdown by autophagy.

Similarly,³⁴ T2DM patients received 3 g resveratrol or placebo daily for 12 weeks. Results were that there was a significant increase in both SIRT1 expression and resting metabolic rate compared with the placebo group. In patients with T2DM, treatment with resveratrol helped regulate energy expenditure, suggesting that resveratrol may have beneficial exercise-mimetic effects.

Again,³⁵ healthy, obese subjects were treated with placebo and 150 mg/day resveratrol for 30 days. The results were that resveratrol increased SIRT1 and improved the muscle’s use of fatty acids as an energy fuel, demonstrating that 30 days of resveratrol supplementation induces metabolic changes in obese humans, mimicking the effects of calorie restriction. Given these results, one might think that resveratrol may aid in weight loss—and indeed this has been shown to be the case in clinical research.

Orlistat is an over-the-counter drug (also known as Alli®) designed to treat obesity by reducing the absorption of fats from the human diet. A study³⁶ was conducted to evaluate the efficacy of combining orlistat with resveratrol in 84 obese subjects over a 6-month period. The subjects consumed a diet with 500 fewer calories than their usual diet for two weeks, and were randomly assigned to four groups, placebo, resveratrol, orlistat, or the O-R combination, and they consumed the energy-reduced diet for 6-months. Results were significant weight loss of 15 lbs in the O-R group compared with 7.7 lbs in the placebo group. Significant decreases in BMI, waist circumference, fat mass, triglycerides, leptin, and leptin/adiponectin ratio were observed with the O-R combination, indicating that it was the most effective weight loss treatment.

In another study,³⁷ 24 patients with metabolic syndrome received resveratrol (500 mg) three times per day before meals for 90 days. Resveratrol administration resulted in significant differences in total weight (P=0.007), body mass index (BMI) (P=0.006), fat mass (P=0.001), and waist circumference (P=0.004). In conclusion, administration of resveratrol significantly decreased weight, BMI, and fat mass.

Blood Sugar/Insulin Resistance
A study³⁸ was conducted using 480 mg/day of resveratrol or placebo for four weeks on 43 patients with diabetes who also had chronic periodontitis (i.e. gum disease). Results were that serum levels of fasting insulin and insulin resistance were significantly lower in the resveratrol group compared with control group. With regard to periodontal disease, there was also a significant difference in the gum pocket depth between intervention and control groups with resveratrol. The researchers recommended that resveratrol supplementation might be beneficial as adjuvant therapy along with non-surgical periodontal treatment in insulin resistance and improving periodontal status among patients with diabetes with periodontal disease.

Another human clinical trial³⁹ was conducted in 32 over-weight, older adults (average age: 73 years). Participants received placebo, 300 mg/day of resveratrol, or 1000 mg/day of resveratrol for 90 days. Results were that, compared to placebo, glucose levels were significantly lower at after treatment among participants receiving either dose of resveratrol (P<0.05), and were well tolerated.

In this study,⁴⁰ 62 patients with T2DM received either an oral hypoglycemic medication, or an oral hypoglycemic medication along with 250 mg/day of resveratrol. Results were that supplementation with resveratrol for three months significantly improved the mean hemoglobin A1c (P<0.05), a measure of long-term glucose control, systolic blood pressure (P<0.05), total cholesterol (P<0.05), and total protein (P<0.05) in T2DM. The researchers concluded that oral supplementation with resveratrol was effective in improving glycemic control and may be a potential adjuvant for the treatment and management of diabetes.

In a pilot study,⁴¹ subjects with impaired glucose tolerance (aged 72 ± 3 years) received 1, 1.5, or 2 g/day of resveratrol for four weeks. After four weeks of resveratrol supplementation, results showed that post-meal (P=0.003) and 3-hour glucose levels (P=0.001) declined. Researchers concluded that, at doses between 1 and 2 g/day, resveratrol improves insulin sensitivity and post-meal plasma glucose in subjects with impaired glucose tolerance. Likewise, in a 4-week study,⁴² T2DM patients received 10 mg/day resveratrol or a placebo. Results showed that, after the fourth week, resveratrol significantly improved insulin sensitivity, which might be due to a resveratrol-induced decrease in oxidative stress that leads to a more efficient insulin-signaling pathway.

Non-Alcoholic Fatty Liver Disease
Nonalcoholic fatty liver disease (NAFLD) refers to the accumulation of fat in the liver of people who drink little or no alcohol. Unfortunately, NAFLD is common—with easily one-third of all American adults being affected⁴³—and often causes no signs and symptoms, and sometimes no complications. In more serious cases, however, the fat that accumulates in NAFLD can cause liver inflammation and scarring.⁴⁴ In addition, NAFLD is usually associated with insulin resistance, central obesity, reduced glucose tolerance, T2DM and high triglyceride levels.

In a clinical study,⁴⁵ 50 NAFLD patients received either a 500 mg/day of resveratrol or a placebo for 12 weeks. Both groups were advised to follow an energy-balanced diet and physical activity recommendations. Results were that resveratrol supplementation reduced alanine aminotransferase (a marker for NAFLD) and hepatic steatosis (fatty liver) significantly more than placebo (P<0E05).

In another study,⁴⁶ 60 NAFLD patients received two 150 mg resveratrol capsules twice daily for three months. Results were that, compared with the placebo group, resveratrol significantly decreased aspartate aminotransferase, glucose and low-density lipoprotein cholesterol (P.0.001) alanine aminotransferase, total cholesterol (P=0.002), and insulin resistance (P=0.016). The researchers concluded that resveratrol supplementation might benefit patients with NAFLD.

Other Resveratrol Benefits
In addition to the aforementioned applications for resveratrol, there are additional benefits for this nutraceutical as well. Two such benefits are related to bone health, and for those who are smokers.

In a clinical study,⁴⁷ 66 middle-aged, obese subjects with metabolic syndrome (average age: 49.3 } 6.3 years) received oral treatment with 1,000 mg or 150 mg of resveratrol, or a placebo daily for 16 weeks to assess changes in the bone turnover marker bone alkaline phosphatase (BAP), and bone mineral density (BMD). Results were that BAP increased dose dependently with resveratrol (P<0.001), compared with placebo. Lumbar spine trabecular volumetric bone mineral density also increased dose dependently with resveratrol (P=0.036), with a significant increase of 2.6 percent in the 1,000 mg resveratrol group compared with placebo (P=0.043). In addition, changes in BAP and bone mineral density were positively correlated (P=0.027).

Smokers typically experience a state of low-grade systemic inflammation and oxidant-antioxidant imbalance. To determine whether resveratrol has beneficial effects on markers of inflammation and oxidative stress, a study⁴⁸ was conducted with 50 healthy adult smokers who alternatively were given 500 mg/ day of resveratrol and placebo. Results were that resveratrol significantly reduced the inflammatory marker C-reactive protein (CRP), triglyceride concentrations, and increased Total Antioxidant Status (TAS) values. The researchers concluded that, because resveratrol has anti-inflammatory, anti-oxidant, and hypotriglyceridemic effects, its supplementation might beneficially affect the increased cardiovascular risk of healthy smokers.

Improving The Bioavailability And Efficacy Of Resveratrol

Now that we’ve reviewed some of the many benefits associated with resveratrol supplementation, let’s briefly consider ways to improve the bioavailability and efficacy of this valuable nutraceutical. First, take resveratrol on an empty stomach. The reason for this recommendation is a study showing that the absorption rate of resveratrol following an oral 400 mg single dose was significantly delayed by the presence of food.⁴⁹

Second, resveratrol may work better when taken together with pterostilbene (a related antioxidant) and quercetin (a flavonoid). In this study,⁵⁰ the antioxidant activities of resveratrol, pterostilbene and quercetin, and the effect of their combination were investigated in human blood cells in-vitro. When used together, the combination protected the blood cells against destruction and against depletion of the important antioxidant, glutathione. Also, the combination of resveratrol with quercetin or pterostilbene synergistically inhibited oxidative injury of membrane lipids. These protective effects may partially explain the health benefit of these bioactive micro-components when together in the diet.

Conclusion
The value of supplementation with resveratrol has moved beyond the “French paradox” and the activation of the SIRT 1 gene, associated with longevity. Human clinical research has demonstrated efficacy of resveratrol for inflammation, immune health/breast cancer prevention, muscle health, cognitive health, weight loss, blood sugar/insulin resistance, non-alcoholic fatty liver disease, and more.

Endnotes

1. Labinskyy N, Csiszar A, Veress G, Stef G, Pacher P, Oroszi G, Wu J, Ungvari Z. Vascular dysfunction in aging: potential effects of resveratrol, an anti-inflammatory phytoestrogen. Current Medicinal Chemistry 2006; 13(9):989–96.
2. Borra MT, Smith BC, Denu JM.Mechanism of human SIRT1 activation by resveratrol. J Biol Chem. 2005 Apr 29;280(17):17187–95. 3. Higdon J, Drake VJ, Steward WP. Resveratrol. Micronutrient Information Center. Linus Pauling Institute, Oregon State University, Corvallis, OR; 2016.
3. Fremont L. Biological Effects of Resveratrol. Life Sci. 2000;66(8):663–73.
4. Soleas GJ, Diamandis EP, Goldberg DM. Resveratrol: A molecule whose time has come? And gone? Clin Biochem 1997;30:91–113.
5. Baur JA, Sinclair DA. Therapeutic potential of resveratrol: the in vivo evidence. Nature reviews. Drug Discovery 2006; 5(6):493–506.
6. Bradamante S, Barenghi L, Villa A. Cardiovascular protective effects of resveratrol. Cardiovasc Drug Rev 2004; 22(3):169–188.
7. Apostolidou C, Adamopoulos K, Iliadis S, Kourtidou-Papadeli C. Alterations of antioxidant status in asymptomatic hypercholesterolemic individuals after resveratrol intake. Int J Food Sci Nutr. 2015 Aug;67(5):541–52.
8. Anisimova NY, Kiselevsky MV, Sosnov AV, Sadovnikov SV, Stankov IN, Gakh AA. Trans-, cis-, and dihydro-resveratrol: a comparative study. Chem Cent J. 2011 Dec 20;5:88.
9. Baur JA, Sinclair DA. Therapeutic potential of resveratrol: the in vivo evidence. Nature reviews. Drug Discovery 2006; 5(6):493–506.
10. Wallerath T, Deckert G, Ternes T, et al. Resveratrol, a polyphenolic phytoalexin present in red wine, enhances expression and activity of endothelial nitric oxide synthase. Circulation 2002; 106(13):1652–8.
11. Imamura H, Yamaguchi T, Nagayama D, Saiki A, Shirai K, Tatsuno I. Resveratrol Ameliorates Arterial Stiffness Assessed by Cardio-Ankle Vascular Index in Patients With Type 2 Diabetes Mellitus. Int Heart J. 2017 Aug 3;58(4):577–83.
12. Pollack RM, Barzilai N, Anghel V, Kulkarni AS, Golden A, O’Broin P, Sinclair DA, Bonkowski MS, Coleville AJ, Powell D, Kim S, Moaddel R, Stein D, Zhang K, Hawkins M, Crandall JP. Resveratrol Improves Vascular Function and Mitochondrial Number but Not Glucose Metabolism in Older Adults. J Gerontol A Biol Sci Med Sci. 2017 Nov 9;72(12):1703–9.
13. Dash S, Xiao C, Morgantini C, Szeto L, Lewis GF. High-dose resveratrol treatment for 2 weeks inhibits intestinal and hepatic lipoprotein production in overweight/obese men. Arterioscler Thromb Vasc Biol. 2013 Dec;33(12):2895–901.
14. Wong RH, Berry NM, Coates AM, Buckley JD, Bryan J, Kunz I, Howe PR. Chronic resveratrol consumption improves brachial flow-mediated dilatation in healthy obese adults. J Hypertens. 2013 Sep;31(9):1819–27.
15. Magyar K, Halmosi R, Palfi A, Feher G, Czopf L, Fulop A, Battyany I, Sumegi B, Toth K, Szabados E. Cardioprotection by resveratrol: A human clinical trial in patients with stable coronary artery disease. Clin Hemorheol Microcirc. 2012;50(3):179–87.
16. Wong RH1, Howe PR, Buckley JD, Coates AM, Kunz I, Berry NM. Acute resveratrol supplementation improves flow-mediated dilatation in overweight/obese individuals with mildly elevated blood pressure. Nutr Metab Cardiovasc Dis. 2011 Nov;21(11):851–6.
17. Magyar K, Halmosi R, Palfi A, Feher G, Czopf L, Fulop A, Battyany I, Sumegi B, Toth K, Szabados E. Cardioprotection by resveratrol: A human clinical trial in patients with stable coronary artery disease. Clin Hemorheol Microcirc. 2012;50(3):179–87.
18. Ghanim H, Sia CL, Abuaysheh S, Korzeniewski K, Patnaik P, Marumganti A, Chaudhuri A, Dandona P. An antiinflammatory and reactive oxygen species suppressive effects of an extract of Polygonum cuspidatum containing resveratrol. J Clin Endocrinol Metab. 2010 Sep;95(9):E1-8.
19. Wong RHX, Evans HM, Howe PRC. Resveratrol supplementation reduces pain experience by postmenopausal women. Menopause. 2017 Aug;24(8):916–22.
20. Samsamikor M, Daryani NE, Asl PR, Hekmatdoost A. Resveratrol Supplementation and Oxidative/Anti-Oxidative Status in Patients with Ulcerative Colitis: A Randomized, Double-Blind, Placebo-controlled Pilot Study. Arch Med Res. 2016 May;47(4):304–9.
21. Samsami-Kor M, Daryani NE, Asl PR, Hekmatdoost A. Anti-Inflammatory Effects of Resveratrol in Patients with Ulcerative Colitis: A Randomized, Double-Blind, Placebo-controlled Pilot Study. Arch Med Res. 2015 May;46(4):280–5.
22. Macedo RC, Vieira A1, Marin DP2, Otton R3. Effects of chronic resveratrol supplementation in military firefighters undergo a physical fitness test–a placebo-controlled, double blind study. Chem Biol Interact. 2015 Feb 5;227:89–95.
23. Espinoza JL, Trung LQ, Inaoka PT, Yamada K, An DT, Mizuno S, Nakao S, Takami A. The Repeated Administration of Resveratrol Has Measurable Effects on Circulating T-Cell Subsets in Humans. Oxid Med Cell Longev. 2017;2017:6781872.
24. Zhu W, Qin W, Zhang K, Rottinghaus GE, Chen YC, Kliethermes B, Sauter ER. Trans-resveratrol alters mammary promoter hypermethylation in women at increased risk for breast cancer. Nutr Cancer. 2012 Apr;64(3):393–400.
25. Chow HH, Garland LL, Heckman-Stoddard BM, Hsu CH, Butler VD, Cordova CA, Chew WM, Cornelison TL. A pilot clinical study of resveratrol in postmenopausal women with high body mass index: effects on systemic sex steroid hormones. J Transl Med. 2014 Aug 14;12:223.
26. Alway SE, McCrory JL, Kearcher K, Vickers A, Frear B, Gilleland DL, Bonner DE, Thomas JM, Donley DA, Lively MW, Mohamed JS. Resveratrol Enhances Exercise-Induced Cellular and Functional Adaptations of Skeletal Muscle in Older Men and Women. J Gerontol A Biol Sci Med Sci. 2017 Nov 9;72(12):1595–1606.
27. Wong RH, Nealon RS, Scholey A, Howe PR. Low dose resveratrol improves cerebrovascular function in type 2 diabetes mellitus. Nutr Metab Cardiovasc Dis. 2016 May;26(5):393–9.
28. Evans HM, Howe PR, Wong RH. Effects of Resveratrol on Cognitive Performance, Mood and Cerebrovascular Function in Post-Menopausal Women; A 14-Week Randomised Placebo-Controlled Intervention Trial. Nutrients. 2017 Jan 3;9(1). pii: E27.
29. Witte AV, Kerti L, Margulies DS, Flöel A. Effects of resveratrol on memory performance, hippocampal functional connectivity, and glucose metabolism in healthy older adults. J Neurosci. 2014 Jun 4;34(23):7862–70.
30. Kennedy DO, Wightman EL, Reay JL, Lietz G, Okello EJ, Wilde A, Haskell CF. Effects of resveratrol on cerebral blood flow variables and cognitive performance in humans: a double-blind, placebo-controlled, crossover investigation. Am J Clin Nutr. 2010 Jun;91(6):1590–7.
31. Moussa C, Hebron M, Huang X, Ahn J, Rissman RA, Aisen PS, Turner RS. Resveratrol regulates neuro-inflammation and induces adaptive immunity in Alzheimer’s disease. J Neuroinflammation. 2017 Jan 3;14(1):1.
32. Konings E, Timmers S, Boekschoten MV, Goossens GH, Jocken JW, Afman LA, Müller M, Schrauwen P, Mariman EC, Blaak EE. The effects of 30 days resveratrol supplementation on adipose tissue morphology and gene expression patterns in obese men. Int J Obes (Lond). 2014 Mar;38(3):470–3.
33. Goh KP, Lee HY, Lau DP, Supaat W, Chan YH, Koh AF. Effects of resveratrol in patients with type 2 diabetes mellitus on skeletal muscle SIRT1 expression and energy expenditure. Int J Sport Nutr Exerc Metab. 2014 Feb;24(1):2–13.
34. Timmers S, Konings E, Bilet L, Houtkooper RH, van de Weijer T, Goossens GH, Hoeks J, van der Krieken S, Ryu D, Kersten S, Moonen-Kornips E, Hesselink MKC, Kunz I, Schrauwen-Hinderling VB, Blaak E, Auwerx J, Schrauwen P. Calorie restriction-like effects of 30 days of resveratrol supplementation on energy metabolism and metabolic profile in obese humans. Cell Metab. 2011 Nov 2;14(5):612–22.
35. Arzola-Paniagua MA, García-Salgado López ER, Calvo-Vargas CG, Guevara-Cruz M. Efficacy of an orlistat-resveratrol combination for weight loss in subjects with obesity: A randomized controlled trial. Obesity (Silver Spring). 2016 Jul;24(7):1454–63.
36. Méndez-del Villar M, González-Ortiz M, Martínez-Abundis E, Pérez-Rubio KG, Lizárraga-Valdez R. Effect of resveratrol administration on metabolic syndrome, insulin sensitivity, and insulin secretion. Metab Syndr Relat Disord. 2014 Dec;12(10):497–501.
37. Zare Javid A, Hormoznejad R, Yousefimanesh HA, Zakerkish M, Haghighi-Zadeh MH, Dehghan P, Ravanbakhsh M. The Impact of Resveratrol Supplementation on Blood Glucose, Insulin, Insulin Resistance, Triglyceride, and Periodontal Markers in Type 2 Diabetic Patients with Chronic Periodontitis. Phytother Res. 2017 Jan;31(1):108–114.
38. Anton SD, Embry C, Marsiske M, Lu X, Doss H, Leeuwenburgh C, Manini TM. Safety and metabolic outcomes of resveratrol supplementation in older adults: results of a twelve-week, placebo-controlled pilot study. Exp Gerontol. 2014 Sep;57:181–7.
39. Bhatt JK, Thomas S, Nanjan MJ. Resveratrol supplementation improves glycemic control in type 2 diabetes mellitus. Nutr Res. 2012 Jul;32(7):537–41.
40. Crandall JP, Oram V, Trandafirescu G, Reid M, Kishore P, Hawkins M, Cohen HW, Barzilai N. Pilot study of resveratrol in older adults with impaired glucose tolerance. J Gerontol A Biol Sci Med Sci. 2012 Dec;67(12):1307–12.
41. Brasnyó P, Molnár GA, Mohás M, Markó L, Laczy B, Cseh J, Mikolás E, Szijártó IA, Mérei A, Halmai R, Mészáros LG, Sümegi B, Wittmann I. Resveratrol improves insulin sensitivity, reduces oxidative stress and activates the Akt pathway in type 2 diabetic patients. Br J Nutr. 2011 Aug;106(3):383–9.
42. Browning JD, Szczepaniak LS, Dobbins R, Nuremberg P, Horton JD, Cohen JC, Grundy SM, Hobbs HH. Prevalence of hepatic steatosis in an urban population in the United States: Impact of ethnicity. Hepatology 2004;40(6):1387–95.
43. Sanyal AJ. American Gastroenterological Association: AGA technical review on nonalcoholic fatty liver disease (national guidelines). Gastroenterology 2002; 123:1705–25.
44. Faghihzadeh F, Adibi P, Hekmatdoost A. The effects of resveratrol supplementation on cardiovascular risk factors in patients with non-alcoholic fatty liver disease: a randomised, double-blind, placebo-controlled study. Br J Nutr. 2015 Sep 14;114(5):796–803.
45. Chen S, Zhao X, Ran L, Wan J, Wang X, Qin Y, Shu F, Gao Y, Yuan L, Zhang Q, Mi M. Resveratrol improves insulin resistance, glucose and lipid metabolism in patients with non-alcoholic fatty liver disease: a randomized controlled trial. Dig Liver Dis. 2015 Mar;47(3):226–32
46. Ornstrup MJ, Harsløf T, Kjær TN, Langdahl BL, Pedersen SB. Resveratrol increases bone mineral density and bone alkaline phosphatase in obese men: a randomized placebo-controlled trial. J Clin Endocrinol Metab. 2014 Dec;99(12):4720–9.
47. Bo S, Ciccone G, Castiglione A, Gambino R, De Michieli F, Villois P, Durazzo M, Cavallo-Perin P, Cassader M.Anti-inflammatory and antioxidant effects of resveratrol in healthy smokers a randomized, double-blind, placebo-controlled, cross-over trial. Curr Med Chem. 2013;20(10):1323–31.
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49. Mikstacka R, Rimando AM, Ignatowicz E. Antioxidant effect of trans-resveratrol, pterostilbene, quercetin and their combinations in human erythrocytes in vitro. Plant Foods Hum Nutr. 2010 Mar;65(1):57–63

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The pungent taste of garlic is not to everyone’s liking, as its odor may remain on the breath and skin for days; moreover, large quantities of ingested garlic, potentially needed to boost immunity may cause gastrointestinal disturbances. The supplement Aged Garlic Extract^TM (Kyolic® AGE^TM) that is odorless, has become a most popular preparation that provides the benefits of garlic, including boosting immunity, without the unpleasant side effects. Moreover, its efficacy and reliable standing as the preferred garlic formulation for research on the health benefits of garlic, has yielded over 700 peer reviewed research publications in scientific and medical journals.

Aged Garlic Extract
The manufacturing of AGE, by Wakunaga of America, consists of harvesting organically grown garlic, and carrying out a procedure of extraction and aging, at room temperature, for 20 months The process converts harsh volatile compounds such as allicin to stable substances, thereby increasing antioxidant levels in AGE above levels found in fresh garlic.

Among the many components in AGE the major ones are organosulfur antioxidants, largely water soluble, and highly bioavailable including S-Allyl cysteine and S-Allyl mercaptocysteine. Also present are lipid soluble organosulfur compounds, carbohydrates, including fructans, which are immuo-boosters, micronutrients such as selenium and other antioxidants such as fructosyl arginine and alixin. The high antioxidant level in AGE prevent the damage induced by free radicals that are generated in metabolism and enhanced by environmental factors, such as radiation of different types including UV light from the sun and UV machines. Free radical damage plays a role in inflammation, and various pathological conditions including heart disease, dementia and cancer, so that the inhibition of free radicals by AGE is part of its action in helping prevent these pathological conditions, in part by boosting immunity.

Our Immune System
A healthy immune system is the secret to good health, protecting against infectious bacteria, viruses, fungi and helping block the development of cancer. A weak immune system exposes us to the damaging effects of infectious bacteria and viruses around us, from direct contact, exposure to a cough or a sneeze, from contaminated food and a wide range of sources that trigger serious illnesses, that may lead to death.

The immune system is complex and multilayered. Inflammation is one of the first responses of the immune system to infection and involves the release of substances called prostaglandins and leukotrienes that attract white blood cells (leukocytes) and interferons, that have anti-viral effects.

Among the white cells, the leukocytes there exist B and T lymphocytes. There are subtypes of T cells: killer T cell that kill cells infected with pathogens and helper T cell that regulate the immune response. Killer T cells kill cells that are infected with viruses (and other pathogens), or are otherwise damaged or dysfunctional. Helper T cells regulate the immune responses directing other cells to perform various tasks. Natural killer cell (NK) have in their power to kill tumor cells. Another group of lymphocytes are ãä-T cells that share the characteristics of helper T cells, killer T cells and NK cells.

AGE Enhances Immunity
Aged Garlic Extract has been shown in preclinical and clinical studies to enhance the immune response, mitigate infectious diseases, and kill cancer cells. AGE intake has been shown to increase the phagocytic (cell-killing) activity of macrophages, the activity of the T lymphocytes and increase the number and action of natural killer cells (NK) and antitumor action; AGE also was found to inhibit the allergy-causing histamine release and have anti-inflammatory effects, suppressing prostaglandins and enhancing interferon.

AGE Increases NK Activity
In a random double-blind clinical trial, Ishikawa and colleagues found that AGE given to patients with colorectal, liver or pancreatic cancer resulted in a significant increase in the number and activity of the NK cells, killing cancer cells.

Advanced-cancer patients with a decline in immune functions and quality of life, with inoperable colorectal, liver, or pancreatic cancer were recruited for the study. In a randomized six month double-blind trial, AGE was given to one group and a placebo to another. The patients consisted of 42 with liver cancer (84 percent), seven patients with pancreatic cancer (14 percent), and one patient with colon cancer (two percent). The study showed that both the number of NK cells and the NK cell activity increased significantly in the AGE group; showing that the administration of AGE to patients with advanced cancer of the digestive system has the potential to improve the anti-tumor NK cell activity.

AIDS patients show lower levels of NK cells. Abdullah and colleagues showed that a six week intake of AGE at 1800 mg/day increased the levels of NK cells to that of healthy individuals; Helper T cells were also increased and patients showed an improvement of several pathological conditions, including herpes virus infection, yeast infections and diarrhea; Comparing the efficacy of AGE to that of fresh garlic, investigators found that AGE was more effective as an immune-stimulator than fresh garlic; NK activity was increased by 160 percent with the intake of AGE capsules compared with an increase of 140 percent in patients taking the fresh garlic preparation.

AGE Helps Reduce Colds And Flu
A randomized, double-blind, placebo-controlled study recruited 120 healthy subjects (60 per group between ages of 21 and 50) and evaluated the effect of AGE supplementation (2.56 g/d) on the proliferation of immune cells and cold and flu symptoms.

After 45 days of intake of an encapsulated Aged Garlic Extract, NK and £^£_-T cells rose in number, compared to placebo. Following 90 days of supplementation, diary entries of illness showed that though the incidence of colds and flu, were not statistically different, the group consuming Aged Garlic Extract showed a reduced severity of both colds and flu noted by a reduction in the number of reported symptoms (21 percent fewer) and by a reduction in the number of days (61 percent fewer), and incidences (58 percent fewer) where the subjects¡¦ function was sub optimal.

The investigators concluded that supplementation of the diet with AGE may enhance immune cell function and potentially reduce inflammation, resulting in a reduced severity of colds and flu.

AGE Blocks Ultraviolet-Induced Immunosuppression.
Studies on human volunteers in Australia found that exposure to ultraviolet radiation (UV) causes immunosuppression resulting in an increase skin cancer frequency. There was a gender difference. UV doses that caused immunosuppression in men were three times lower than those causing immunosuppression in women. The investigators concluded that this phenomenon might underlie the higher incidence of skin cancer and mortality observed in the male population.

In a preclinical study, where the immune response as measured by contact hypersensitivity, Reeve and colleagues found that immunosuppression of 58 percent induced by a moderate exposure to UVB radiation was reduced to 19 percent by a diet containing AGE, at 4 percent of the diet. The preclinical studies suggest that AGE may help protect humans against immunosuppression induced by exposure to UV, and therefore have a potential to reduce the risk of UV induced skin cancer, for example by lengthy exposures to the sun.

AGE Reduces Inflammatory Prostaglandins
Oxidative damage by free radicals and immune-inflammatory activation are considered important factors in the development of cancer, neurodegenerative and cardiovascular diseases. Prostaglandins are substances associated with inflammation in that the release of local pro-inflammatory prostaglandins takes place, accompanied by the destruction of tissue. Rahman and colleagues have shown that dietary supplementation with AGE for 14 days reduced the plasma and urine levels of prostaglandin 8-iso-PGF (2 alpha) by 29 and 37 percent, respectively in nonsmokers and by 35 and 48 percent, respectively in smokers.

By stopping the intake of AGE, they found that in both groups, smokers and non smokers, the plasma and urine concentrations of prostaglandins reversed to values that were no different from those before ingestion of AGE, within fourteen days after cessation of the dietary supplementation. The study shows that a continuous intake of AGE is required to maintain the reduced levels of inflammatory prostaglandins.

The Bottom Line
Aged Garlic Extract is a powerful wide ranging health supplement that plays a role in helping enhance immunity and thus helping protect against diseases and conditions that involve inflammation and weakening of the immune system; such conditions have been reported to be associated with cancer development, neurodegenerative and cardiovascular disease as well as aging. In over 700 medical and scientific studies in both preclinical and clinical studies, AGE has shown its capacity to help reduce disease and maintain health.

References

1. Nantz MP, Rowe CA, Muller CE et al Supplementation with aged garlic extract improves both NK and Υδ-T cell function and reduces the severity of cold and flu symptoms: a randomized, double-blind, placebo-controlled nutrition intervention. J Nutr. 2012; 31:337—44.
2. Borek C. Dietary antioxidants and human cancer. Integr Cancer Ther. 2004;3:333—41.
3. Reeve VE1, Bosnic M, Rozinova E, Boehm-Wilcox C. A garlic extract protects from ultraviolet B (280¡V320 nm) radiation-induced suppression of contact hypersensitivity. Photochem Photobiol. 1993;58:813—7.
4. Dillon SA, Lowe GM, Billington D, Rahman K. Dietary supplementation with aged garlic extract reduces plasma and urine concentrations of 8-iso-prostaglandin F(2 alpha) in smoking and nonsmoking men and women. J Nutr. 2002 ;132:168—71.
5. Ishikawa H, Saeki T, Otani T, Suzuki T, Shimozuma K, Nishino H, Fukuda S, Morimoto K. Aged garlic extract prevents a decline of NK cell number and activity in patients with advanced cancer. J Nutr. 2006;136:816S—820S
6. Abdullah TH, Kirkpatrick DV, Carter J. Enhancement of natural killer activity in AIDS with garlic. J Oncology. 1989;21:52—3.

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Focus on the Prostate

Pollen extract is a special mixture of both water-soluble and fat-soluble compounds derived from various pollens, chiefly rye, and often marketed under the name Cernilton. Most people know of pollen extracts in conjunction with prostate health. This generally is associated with benign prostatic hyperplasia (formerly called hypertrophy), which involves a renewed growth in the number of prostate cells late in life.¹ Unfortunately, of men between the age of 40 and 59, nearly 60 percent can be shown to already be suffering from benign prostatic hyperplasia. This usually does not present a noticeable problem until after the age of 50; by the age of 80, however, some 85 percent of all men suffer from one or more symptoms of BPH. The primary effect of BPH is a progressive decrease in the ability to empty the bladder as the prostate enlarges and applies pressure to the urethra. The American Urological Association Symptom Index is now a standard assessment for BPH severity.

Prostatitis is really a catch-all term for several types of prostate problems.² It always involves inflammation of the prostate and may also include considerable pain, whereas BPH may not involve any pain at all (as opposed to discomfort). Prostatitis is fairly common in adult males and has been classified into four types. Only at most five percent of all cases consist of either acute or chronic bacterial prostatitis, i.e., cases in which infection and the aftermath of infection are the main issues. Non-bacterial prostatitis comprises 64 percent of cases and Prostatodynia makes up another 31 percent.

Non-bacterial prostatitis is the most common of the prostatic conditions, but its cause has not been isolated. It is characterized by an unusually high number and activity of inflammatory cells in the prostate. The resulting inflammation resembles that found in chronic prostatitis, but there is no history of infection nor do cultures (for bacteria) prove positive. Conventional medical treatments do not yield good results. Abstaining from alcohol and spicy foods helps in some cases.

Prostatodynia, which is most common in young and middle-aged men, presents many symptoms similar to the above, but lacks the excessive number of inflammatory cells. Just as nonbacterial prostatitis has some symptoms that are peculiar to it, so, too, does prostatodynia. In particular, pain and/or discomfort in the groin, perineum, testicles, lower back and penis seem to characterize this condition. Smooth muscle spasms in the prostatic portion of the urethra and in the neck of the bladder are at work here. The subsequent reflux of urine into prostatic and ejaculatory ducts causes a chemically-induced inflammation. Fatigue in the muscles in the pelvic region and emotional stress appear to be powerful contributory factors in prostatodynia.

Of these three conditions, BPH is what concerns most men. Prostate enlargement is strongly related to normal aging. Some of the factors involved are quite well understood. Nevertheless, there also is substantial disagreement about other issues. BPH can be called an aspect of male menopause because an increased ratio of estrogen to testosterone is active in BPH just as, conversely, in women passing through menopause the ratio of testosterone to estrogen increases. Testosterone, the “male” hormone, is at its peak during adolescence. It decreases thereafter, and the rate of decrease sharpens by about age 50. The decline in testosterone production typically calls into play the compensatory release of other hormones, which are stimulants to testosterone production. These cannot prevent the decline in testosterone levels, but they can lead to an elevated rate of transformation of testosterone into 5-alpha-dihydrotestosterone (DHT) and to the increased binding to and/or decreased clearance of DHT from prostate cells. Testosterone is converted to DHT by the enzyme 5-alphareductase. Ultimately, it is DHT’s actions that cause the enlargement of the prostate. DHT binds to specific receptors on the prostate cells, the alpha 1-receptors. It then is transported into the nucleus of these cells where it attaches to the DNA and ultimately turns on prostate growth.

How do pollen extracts work? Clinical trials with these extracts covering 12 weeks of treatment generally have produced improvements in cases of BPH and prostatodynia of between 60 and 88 percent when adequate dosages were administered and depending upon the severity of the starting condition. The first mechanism of action is smooth muscle relaxation, something that promotes the ability to urinate as spasms in the smooth muscle tissues are reduced. In animal studies, pollen extracts have been shown to inhibit urethral contraction, which facilitates the discharge of urine. Data in these studies is consistent with the observations that pollen extracts facilitate voiding of the bladder and reduce residual urine.

A number of clinical studies have shown that the pollen extracts reduce the size of the prostate in those individuals suffering from BPH. These data indicate that pollen extracts should either inhibit the formation of DHT by blocking the alpha-reductase enzyme, or act to block the binding of DHT to the alpha 1-receptor and thus improve the clearance of DHT from the prostate. Either mechanism could be effective in blocking the DHT-induced biological cascade that leads to prostate enlargement.

Inflammation, Immune Functions and the Liver

Inflammation underlies a large number of conditions, including several of those improved by pollen extracts. Evidence to support the anti-inflammatory action of the pollen extracts comes from both animal and clinical experience. Three animal studies indicated that pollen extracts exhibit anti-inflammatory activities. The first showed that pollen extracts inhibit the arachidonic acid cascade, a primary generator of free radicals in the tissues. The second indicated that orally administered pollen extracts counteract the inflammatory process found with artificially-induced liver damage in rats. The third showed that an induced inflammatory condition in rodents was significantly reduced by pollen extracts. It has been proven that pollen extracts are active in human subjects against inflammation. As noted already, several clinical studies also have shown that pollen extracts are an effective treatment for the inflammatory prostate conditions prostatitis and prostatodynia.

Mechanisms of action involving inflammation link pollen extracts to conditions that involve more than just the prostate. It has long been known that pollen extracts modulate the actions of the immune system. Many years ago, researchers showed that the water-soluble fraction selectively inhibits the growth of some prostate cancer cell lines. Later research was published, which showed that a compound found in the water-soluble fraction does not merely inhibit prostate cancer cell growth, but actually causes the death of these cells.³ These results were found in vitro studies (that is, in cultured cells), yet they provide promise for research to come.

The liver protective effects of pollen extract, which have been researched over the years, have received another boost from scientists in the Ukraine. In this case, the tests were in vivo, that is, with animals using a special extract of bee-collected pollen. First, it was established that small doses of x-ray radiation cause oxidative damage to fats in the liver (lipid peroxidation) and that this damage activates antioxidant enzyme protective systems. Next, it was discovered that the introduction of pollen extract into the animals’ systems normalized the activity of the glutathione enzyme system, one of the most important of the body’s in-built antioxidant systems.⁴

Immune Functions for the Heart and Recovery

Surprisingly, pollen extracts may possess the ability to protect the heart against certain types of assault. The ability of pollen extract to protect the cardiovascular system against free radical damage was demonstrated over a decade ago. Now, taking research in a quite different direction, it has been shown that the damage to the heart that can be caused by excess adrenaline also can be reduced by the use of the water-soluble fraction of the pollen extract.⁵ Researchers admit that they do not have a good explanation for how this cardio-protection is achieved; yet their findings open up the possibility for totally new uses for pollen extract in the future!

Similar to the cardiac protection afforded is general immune protection. Although primarily known as treatments for BPH, flower pollen extracts have been thoroughly studied for their anti-inflammatory properties and their abilities both to boost flagging immune functions.⁶ One of the findings of this research is that pollen extracts act as immuno-regulators and can reduce immune hyperactivity. The serious reader can work through the earliest literature on the development of pollen extracts in Europe and discover that the early uses of pollen extracts were a) for recovery during convalescence and b) recovery from sports exertions.

Conclusions
Pollen extracts have turned out to be surprisingly versatile in their range of health benefits. Along with the prostate benefits, there further are general immune benefits, effects on cancer, the liver, sports recovery and much more.⁷ Every man aged 50 and above probably should consider a pollen extract supplement as insurance against BPH and other prostate issues. However, given the range and variety of benefits associated with pollen extracts, there is a good argument to be made for men to supplement with pollen extracts for general protection against over-training and or supporting immune imbalance.

References

1. 1 F. Hinman, Benign Prostatic Hypertrophy. New York: Springer Verlag, 1983.
2. 2 E.M. Meares, Jr., “Prostatitis and Related Disorders,” in Campbell’s Urology, 6th edition, ed. by P.C. Walsh, et al. Philadelphia, PA: W.B. Saunders Company, 1992, pp. 807–22.
3. 3 Roberts KP, Iyer RA, Prasad G, Liu LT, Lind RE, Hanna PE. “Cyclic hydroxamic acid inhibitors of prostate cancer cell growth: selectivity and structure activity relationships.” Prostate 1998 Feb 1; 34(2):92–9.
4. 4 Bevzo VV, Grygor’eva NP. [Effect of bee pollen extract on glutath one system activity in mice liver under X-ray irradiation]. [Article in Ukrainian] Ukr Biokhim Zh 1997 Jul-Aug; 69(4):115–7.
5. 5 Polanski M, Okon K, Przybylo R, Frasik W. Cardioprotective properties of hydrophilic pollen extract (HPE). Polish Journal of Pathology 1998; 49(2):109–12.
6. 6 Samochowiec L, et al., “General immunological properties of fat soluble (Cernitin GBX) and water-soluble (Cernitin T60) pollen extracts,” European Journal of Pharmacology 183, 3 (1990) 906.
7. 7 Graminex_Clinical_Studies_Index found at http://www.readbag.com/pollenaid-pollenaid-file-graminex-clinical-studies-index.

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These include smoking, alcohol use and others. The surprising fact is how your oral health has a connection to breast cancer. You may be 11 times more likely to develop breast cancer if you have poor oral health or gum disease. Journal of Breast Cancer Research and Treatment conducted a survey of 3,273 people and found that individuals with chronic periodontal disease (gum disease) had a higher occurrence of breast cancer.

Another study was reported by the World Health Organization (WHO) and was conducted between 1985 to 2001. This study also concluded that gum disease increases the risk of breast cancer.

Gum disease has been linked to several general health chronic illnesses, including pneumonia, prostate cancer, stroke, heart disease, problem pregnancy, diabetes and breast cancer.

• Pneumonia: Bacteria in the oral cavity can be aspirated into the lungs and cause respiratory diseases including pneumonia.
• Prostate cancer: In 1986, over 48,000 men were involved in a study conducted by Dr. Dominique Michaud, Imperial College of London. The study concluded gum disease increases the risk of prostate cancer by 14 percent.
• Diabetes: According to the American Academy of Periodontology, diabetic patients are more likely to develop gum disease, which in turn can increase the risk of infection.
• Heart disease: Researchers have found that people with gum disease are almost twice as likely to suffer with coronary artery disease as those without it. As oral bacteria enters the blood stream, it attaches to fatty plaques in the heart blood vessels and contributes to clot formation. These blood clots can then obstruct normal blood flow, which can lead to heart attack.
• Pregnancy problems: Pregnant women who have gum disease may be more likely to have babies that are born too early and too small.

Connecting the Dots
In general, gum disease causes inflammation. Inflammation has been found to be the precursor of heart disease, stroke, pregnancy problems and over all fatigue. In other words, it is a marker for generalized ill-health. This has been confirmed through blood work and C-reactive protein. C-reactive protein is a inflammation marker which decreases when gum infection is brought under control, and increase with advanced gum disease.

Inflammation: The Warning Sign Not to be Ignored
The first sign of gum disease is inflammation. You’ll know when this is present as your gums appear slightly red, tender, and may even bleed when you brush or floss. The main cause of inflammation is bacteria that form a film called plaque, and stick to the gum and teeth surfaces. If this plaque is not removed at least once per day, the problem can advance to severe gum disease. As inflammation advances, the disease effects destruction of the gums and eventually bone. The teeth develop tooth decay, become loose and may have to be extracted. This is why dental visits are very important at least every three months to monitor the health and condition of your teeth and gums, especially with the presence of cancer.

The bacteria that causes gum disease forms a thin biofilm called plaque and accumulates on the gums and teeth. This same bacteria is found in hardened plaque in arteries that lead to arteriosclerosis. A study by the Karolinska Institute reported the bacteria in gum disease can result in the Epstein-Barr virus and cytomegatocirus. These viruses may result in the suppression of the body’s immune system, which can contribute to the incidence of breast cancer.

There are other connections between breast cancer and oral health. Chemotherapy and radiation may be used to kill or slow breast cancer cells by interfering with growth and multiplication of cells. If chemotherapy or radiation is prescribed as part of treatment for breast cancer, side effects can be severe and include:

• Mucositis, a severe form of inflammation of the mouth.
• Increase risk of infection in the mouth. If the drug suppresses white cells, which normally protect against infection, deep cleanings and other invasive procedures such as tooth extraction can result in infection.
• Difficulty in swallowing.
• Taste alterations ranging from unpleasant to tasteless.
• Due to dry mouth, difficulty with speech and eating.
• Oral yeast infection from the fungus candida.
• Poor nutrition due to difficulties in eating, dry mouth or loss of taste.
• Deep aching and burning pain that mimics toothache.

Most patients are treated with chemotherapy or radiation. However, some patients may be treated with bisphosphonates, such as Fosamax, Boniva, and others. Recent studies from University of Southern California suggest long-term use of such bisphosphonates may develop into destruction of the jaw bone. The risk is low but increases with chemotherapy.

How to Minimize Side Effects
Most people are aware of hair loss with chemotherapy. But most don’t realize that more than one-third of people being treated for breast cancer can develop complications that affect the mouth. These complications can affect your quality of life. Preexisting or untreated oral disease can even complicate cancer treatment. This is one reason to make sure you visit your dentist at least one month before beginning cancer treatment.

The mouth is made of cells that renew themselves daily. Since chemotherapy and radiation target certain types of cells that regenerate quickly even under normal circumstances, your mouth will be susceptible to damage. If you minimize bacterial plaque buildup by practicing good hygiene, you can decrease the side effects of treatment for breast cancer. The following recommendations are important to follow:

1. Brush with a soft toothbrush or sponge brush to clean your teeth and gums.
2. Floss gently.
3. Only use alcohol-free mouthwash, preferably one free of saccharin, but one containing xylitol.
4. When white blood cells counts are reported by your physician to be low, avoid dental treatment.
5. Avoid dental treatment for about a week after chemotherapy.
6. Inflammation starts with red gums that may bleed. Even slight bleeding should not be ignored.
7. Use toothpaste and chewing gum with xylitol.
8. Regular dental visits to identify problems before they develop.
9. If you wear dentures, make sure you keep them clean and that they fit well. Make sure to take them out at night.

The post Breast Cancer and Oral Health appeared first on Total Health Magazine.

Unlike the health challenges of the past, which were predominantly due to infectious diseases, our modern health epidemics such as cardiovascular disease, diabetes, dementia, cancer, and obesity are fueled by a one-two punch of chronic inflammation and extensive free radical damage to our cells.

The Challenge of Inflammation and Free Radical Damage
In the world of medicine, it is now accepted that inflammation and free radical damage are two of the greatest threats to our health.

Inflammation is part of the body’s natural defense against irritation, toxic foods and chemicals, infections and other foreign invaders. However, there are times when the appropriate immune response to subdue infections, allergies and toxins is disrupted. The immune system can then shift into a chronic state of inflammation, which is now recognized as a major factor in most chronic health problems.

Free radicals are the other great threat, causing a condition known as oxidation, or oxidative stress. In the material world oxidation is observed as rust; and a similar process occurs within our bodies. Dr. Ames, from the University of California, Berkeley believes, “Free Radical Oxidant by-products of normal metabolism cause extensive damage to DNA, proteins, and lipids.” He argued that this damage is a major contributor to aging and to degenerative diseases such as cancer, cardiovascular disease, immune system decline, brain dysfunction, and cataracts.

Oxidative stress and inflammation are intimately connected, each fueling the other. A vicious cycle is created: free radical damage leads to inflammation and inflammation causes free radical damage.

The key to recovering and preserving our health requires both the quenching of inflammation and the prevention of excessive free radical damage. While many options abound, what is the most effective way to protect against both inflammation and free radical damage?

Nutrition from the East Meets Innovation from the West The best solutions to the problems caused by our modern industrialized world come from Mother Nature; but it took a healthy dose of modern innovation and sound science to unlock her true potential.

Eastern medicine has long known that the seeds of nutritionally rich plants like black cumin, black and red raspberries, Chardonnay grapes, pomegranates, blueberries and cranberries contain exceptional amounts of vital health-promoting nutrients. For instance, black cumin has been used for more than 3000 years for its immune system strengthening properties, but it has only been scientifically investigated for the past 40 years. Since then, more than 200 studies have revealed the secrets of its extraordinary healing properties.

The oils from black cumin seeds are exceptionally nourishing, as they are loaded with antioxidants and essential fatty acids (EFAs). In addition, they contain nigellone, which works as an antihistamine to provide allergy relief, and thymoquinone, which has strong anti-inflammatory properties. Another natural powerhouse of nutrition is found in black raspberry seed oil. It is also nutritionally rich, and has powerful anti-inflammatory properties. It contains dozens of powerful antioxidants, as well as high amounts of omega-3 and omega-6 essential fatty acids. Modern science shows us that when combined, black cumin and black raspberry seed oils actually enhance each other, and the result is a terrific synergy that powerfully counteracts both inflammation and free radicals.

Modern innovation has also unlocked the solution to harnessing these oils in their most powerful state. The traditional processing methods employ either high heat or harsh chemicals to separate the seed oils from the flours, but these methods either damage valuable nutrients or contaminate the final products. Fortunately, the development of a chemical-free NatureFRESH Cold-Press™ technology has solved the problem. It gently presses and separates the seeds into oils and flours at low temperatures in an oxygen-free environment. The results are natural ingredients exhibiting unprecedented nutrient concentrations that preserve all of nature’s potency, purity and freshness.

What do you get when you combine the nutritional synergy of concentrated black cumin and black raspberry seed oils with the NatureFRESH Cold-Press technology? You get a superstar health product called Immuno-Viva® Core, providing comprehensive heart, immune and inflammatory support. This synergy is truly unsurpassed as a two-pronged solution for the two most pressing health needs—comprehensive anti-inflammatory support, and antioxidant protection for the entire body.

Balancing the Immune System
Essential fatty acids, as the name implies, are essential for good health, yet a staggering 99 percent of Americans are deficient in them. Why is this a problem? Because EFAs like omega-3 and omega-6 are needed by the body to support immune function, inflammation control, the uptake of nutrients, weight regulation, energy levels, fertility, bone strength, the balance of hormones and mood, regulation of gene expression, and brain, eye, skin and hair health. They are important building block to health, and Americans are not getting enough.

Even more important than the total amount of EFAs we take in is the ratio between the types of EFAs we get from our food. This is where the average American diet really fails us. Experts researching the dietary ratio of omega-6 to omega-3 fatty acids, suggest that in early human history the ratio was about 1:1. Currently most Americans have a dietary ratio that falls between 20:1 and 50:1, while an optimal diet should consist of roughly two–four times more omega-6 fatty acids than omega-3 fatty acids. This ratio imbalance and our overall lack of omega-3 in our diet can be boiled down to this: an omega-3 deficiency may be the single most widespread, health-damaging physical cause of degenerative diseases of our time.

This is where Core comes to the rescue. Its proprietary formulation provides all the necessary essential fatty acids (omega-3, -6, and -9) required on a daily basis, but it has an ideal omega-6/omega-3 ratio of 2:1. Not only that, but it also combines these EFAs with powerful lipid soluble antioxidants. The problem with most EFAs, such as those found in flax and fish oils, is their susceptibility to free radical damage which causes them to quickly become rancid. Core’s potent antioxidants, however, protect the EFAs and keep them stable for over 18 months.

The Highest Amounts of Lipid Antioxidants
Antioxidants are the body’s defenders against free radical damage. In the past we have generated adequate antioxidants from a bountiful diet of fruits and vegetables. However, it is estimated only 10 percent of the U.S. population consumes five servings of fruits and vegetables per day. Our nutrient deficient diets as well as on-going physiological and environmental stressors put us in desperate need of more antioxidant protection.

The unique synergy between black cumin and black raspberry seed oils has resulted in an exceptionally high number of lipid soluble antioxidants, which are the most active in protecting cell membranes from free radical attack. According to Dr. Arnold S. Leonard, a cancer researcher and retired professor of surgery at the University of Minnesota Medical School who has been studying Immuno-Viva Core:

“The real key is the number of different types of antioxidants Core contains. It has dozens of different antioxidants, including, all eight forms of vitamin E. The result is a powerful synergism. In other words, the combination of antioxidants found in Core is much more beneficial than the sum of its parts.”

In fact, Core has more antioxidant diversity than probably any other product available today, and it has 10 times more antioxidants than flax seed oil. (See chart.) This high antioxidant capacity combined with the potent EFAs make Core a unique health product that can help our bodies counteract the problems associated with free radicals and inflammation.

Nature’s Power Supported by Science
Many scientific studies now confirm that Core’s blend of EFAs and antioxidants gives it superior capability of supporting the immune system by providing protection from free radical damage and by enhancing anti-inflammatory function. In addition, research shows Core offers powerful support for heart health by lowering LDL cholesterol and diastolic blood pressure.

There have been many lab and clinical studies investigating the benefits of Immuno-Viva Core, and their results have revealed that:

• Core contains a powerful synergistic blend of diverse antioxidants.
• Both ingredients in Core have been shown to be Cox-2 inhibitors over 200 times stronger than aspirin.
• In lab studies, Core helped boost immune response when under attack, elevating CD8 and NK cell counts.
• Core can help lower LDL cholesterol and diastolic blood pressure, supporting vital heart functions.

Mounting scientific evidence extols the many health benefits of omega-3s and antioxidants. The FDA has approved claims that omega-3 may reduce the risk of heart disease, and that antioxidants can improve immune function. And countless studies have shown the benefits of these nutrients when given to people undergoing chemotherapy or suffering from arthritis or autism or obesity, or countless other conditions.

But perhaps the most important research is focusing on prevention. Core’s dual solution—comprehensive antiinflammatory support and antioxidant protection—can help comprehensively improve our natural defenses, and that makes staying healthy in the 21st century a whole lot easier. For more information visit www.immumo-viva.com, or talk to your health care professional.

The post Nature’s FREE RADICAL INFLAMMATION Solution appeared first on Total Health Magazine.