**Post written by Dr. Puya Yazdi, MD, Medical Director for Cyvex Nutrition

The potential health benefits of red wine on the cardiovascular system are now commonly known.  In fact, in the previous post “Savor the Polyphenols” (click to view post), we discussed how modern science and medicine believe that this nutritional benefit is derived from the polyphenols found in red wine. Studies have shown that polyphenols can improve cardiovascular health: first, by helping the body release nitric oxide which leads to a reduction in blood pressure; second, by reducing circulating levels of total cholesterol and LDL or so called “bad cholesterol”; third, by decreasing plaque formation and LDL oxidation, two mechanisms that can lead to clogging of arteries; and finally, by acting as an anti-oxidant and thereby preventing the damage caused to cellular make-up as a result of free radicals that accumulate during the aging process, which are a normal but unwanted by-product of metabolism.*

Just recently, a novel scientific paper was published by a team of researchers from the University of Strasbourg in France on the benefits of red wine polyphenols. Specifically, this research group led by Valérie Schini-Kerth decided to study the potential benefits of red wine polyphenol consumption as it relates to aging and the decline of vascular endothelium function and exercise capacity. The endothelium is the thin layer of cells that lines your blood vessels.  The normal functions of endothelial cells include enabling coagulation, platelet adhesion and immune function. Endothelial dysfunction is associated with reduced anti-coagulant properties and the inability of arteries and arterioles to dilate fully, and the decline of endothelial cell function during the aging process is a very prominent mechanism that can lead to cardiovascular disease.*

First, as previously stated many epidemiologic studies have demonstrated a strong benefit to a healthy lifestyle with red wine consumption and specifically red wine polyphenols. In order to test the potential benefit of long term polyphenol consumption on the aging-related decline of vascular endothelium function and exercise capacity, the researchers created a well-designed and controlled animal study.  Starting with rats aged 16 weeks and continuing until the rats were 40 weeks, the researchers divided the rats into four groups: Group one received 3 percent ethanol as a control; groups two and three received 25 or 75 mg of red wine polyphenols per kg of body weight per day in 3 percent ethanol; and the final group received the antioxidant and NADPH oxidase apocynin at 100 mg/kg/day in 3 percent ethanol.

The results were quite startling. The researchers found that both polyphenol groups and the apocynin group showed significantly lower levels of aging-induced vascular oxidative stress in the endothelium. Furthermore, the high dose polyphenol group, but not the lower dose group, displayed less of a decline in physical performance, compared to the control animals in exercise capacity. The researchers clearly concluded that not only does polyphenol consumption slow down the decline in endothelium function and exercise capacity seen during the aging process, but also that the more polyphenols consumed, the slower the decline and hence the greater the benefit to the cardiovascular system.*

This latest groundbreaking work from France is one of the most recent examples of scientific and medical literature in support of polyphenols playing a prominent role in maintaining a healthy cardiovascular system. In addition, to this latest animal study, we have numerous epidemiologic studies, cell culture work, and clinical studies demonstrating a positive role of polyphenols on the cardiovascular system. The most important thing to take from this recent study is that not only can polyphenols help to maintain a healthy cardiovascular system, but also that their long term consumption can help to slow down the normal aging process. Clearly, it is slowly becoming time for these compounds to take their place alongside your fruits, vegetables, and healthy grains in proper nutrition and health.

References:

S. Dal-Ros, J. Zoll, A. Lang, C. Auger, N. Keller, C. Bronner, B. Geny, V. Schini-Kerth (January 2011).  “Chronic Intake of Red Wine Polyphenols by Young Rats Prevents Aging-Induced Endothelial Dysfunction and Decline in Physical Performance: Role of NADPH Oxidase”. Biochemical and Biophysical Research Communications. 404 (2):743-749

*These statements have not been evaluated by the Food and Drug Administration.  This product is not intended to diagnose, treat, cure or prevent any disease.

Author’s bio:  Puya Yazdi, MD, Medical Director for Cyvex Nutrition, has nearly six years of experience in the medical and scientific fields in addition to working in the business sector as an advisor and consultant. He holds an MD degree from The University of Southern California and a BS degree from the University of California, Irvine in Biological Sciences. Puya underwent medical and scientific training at Stanford University and is currently undergoing further training at UC Irvine.

**Blog post by Puya Yazdi, MD, new Medical Director for Cyvex Nutrition

For years physicians, nutritionists, and even our televisions, have warned us against the risks associated with eating high fat diets, specifically, the risk of cardiovascular disease (CVD). Cardiovascular disease continues to be a leading cause of morbidity and mortality among adults in Western countries. By now, many of us are fully aware of the leading risk factors: cigarette smoking, high blood pressure, high serum total cholesterol and LDL-cholesterol, low serum HDL-cholesterol, diabetes mellitus, high fat diet and advanced age. Yet there has always been one small but important caveat to the standard medical doctrine. Dr. Serge Renaud, a scientist from Bordeaux University in France, even coined a term for this caveat: the “French Paradox.” The French people eat an extremely high fat diet, have higher rates of cigarette smoking, get less exercise than an average American, and yet have substantially lower rates of cardiovascular disease. The question remains: why? Over the last twenty years, we have been slowly approaching our answer.

Over the years, numerous studies have linked a diet rich in fruits and vegetables with a reduction in CVD risk factors. This is presumably due to the presence of, in plant foods and certain beverages, a variety of compounds including an array of antioxidants, such as vitamin C, vitamin E, polyphenols and carotenoids. Polyphenols in particular have been associated with a reduction to the risk of different diseases in several studies. The French Paradox has been ascribed to the consumption of red wine. This effect has been attributed mainly to the presence of polyphenols, a large group of compounds present in plant foods and beverages that have demonstrated strong antioxidant capacity. Furthermore, the alcohol in wine (Ethanol) can also improve the bioavailability of polyphenols, as well as play a specific cardioprotective role.*

These observations and hypotheses have led to physicians and scientists conducting numerous studies involving cells, animals, and human subjects to try to determine what the true power of grape extracts on cardiovascular health are.  So what have we learned about the true power of grape extracts? A lot, and the scientific data and conclusions point to a definite role that grape extracts can play in improving cardiovascular health.

First, numerous animal and human studies have demonstrated that grape extracts can reduce blood pressure. This is mainly a result of the polyphenols found in grape extracts. Specifically, it has been suggested that grape polyphenols promote the release of Nitric Oxide (NO), a compound with vasorelaxing and anti-aggregating effects and, that in the long term, induces the expression of protective genes for the cardiovascular system. Said less scientifically, polyphenols help the body release NO which leads to veins relaxing, thus lowering blood pressure, while also entering the body’s cellular workings and hence causing DNA to start expressing, i.e. making mRNA that becomes proteins, genes that help protect your body.*

Second, grape extracts have been shown to have a hypolipidaemic (by that we mean they help reduce the numerous fats circulating in your blood) effect, reducing levels of plasma total cholesterol and LDL-cholesterol, which is the body’s bad cholesterol. This effect of polyphenols would be related to the fact that these compounds may absorb cholesterol, bile acids and other dietary lipids and hence help the body get rid of them.*

Third, grape extracts have a definite anti-atherosclerotic effect in the early stages of development of atherosclerosis, observed as a reduction in atheromatous plaque and in LDL oxidation. This just means that grape extracts can fight the dangerous plaques that build up in our arteries before they form. Simply stated, oxidation of LDL can lead to plaque formation in our arteries, which is accompanied by smooth muscle cells proliferating and increasing the plaque. Grape extracts appear to prevent LDL from being oxidized and prevent the smooth muscle cells from increasing, fighting atherosclerosis by means of two different but equally powerful mechanisms.*

Finally, grape extracts show an improvement in antioxidant status measured in terms of plasma antioxidant capacity, oxidation biomarkers, antioxidant compounds and antioxidant enzymes. It has become increasingly clear over the last twenty years that our bodies comprise a delicate balance between the reactive oxidation products that form as a result of necessary biochemical processes and our bodies’ antioxidant capabilities to prevent these reactive oxidation products from causing damage to cells, proteins, and even our DNA. Grape extracts help the body defend against these dangerous products that have been implicated in such conditions as cardiovascular disease, diabetes, and even cancer.*

What started as a simple observation by Dr. Renaud over twenty years ago has led to an explosion of clinical and scientific research conducted by some of the leading scientists and physicians from around the world on the inherent power found in grape extracts. There will be many future studies to discover even more about the mechanisms behind grape extracts’ ability to aid in cardiovascular health, but from a health standpoint it is clear that they represent an extremely powerful ingredient to help protect us from the risks and dangers associated with cardiovascular disease.

References:

Ferrieres, J. (2004). “The French Paradox; Lessons for other countries”. Heart 90 (1): 107–111.

Arts, IC & Hollman, PC (2005) Polyphenols and disease risk in epidemiologic studies. Am J Clin Nutr 78, Suppl. 1, 559S–569S

Lekakis, J, Rallidis, LS, Andreadou, I, et al.. (2005) Polyphenolic compounds from red grapes acutely improve endothelial function in patients with coronary heart disease. Eur J Cardiovasc Prev Rehabil 12, 596–600.

Zern, TL, Wood, RS, Greene, C, et al.. (2005) Grape polyphenols exert a cardioprotective effect in pre- and post-menopausal women by lowering plasma lipids and reducing oxidative stress. J Nutr 135, 1911–1917.

*These statements have not been evaluated by the Food and Drug Administration.  This product is not intended to diagnose, treat, cure or prevent any disease.

Author’s bio:  Puya Yazdi, MD, Medical Director for Cyvex Nutrition, has nearly six years of experience in the medical and scientific fields in addition to working in the business sector as an advisor and consultant. He holds an MD degree from The University of Southern California and a BS degree from the University of California, Irvine in Biological Sciences. Puya underwent medical and scientific training at Stanford University and is currently undergoing further training at UC Irvine.

** By Anh Thu V. Tran- Medical Director & Nutrition Consultant, Cyvex Nutrition

From the light- to medium-bodied prancing to the puckering power boldly dancing, full-bodied reds, aired, swirled, and sipped, experiencing each dynamic flavor from plum to currant to smoke and so forth, red wine in its nature not only provides a taste like no other, but also has been well supported to hold health benefits with moderate consumption.  Despite diets of high amounts of saturated fats including butter and cheese, the paradox goes, the French have a relatively low incidence of cardiovascular events, which many have attributed to regular drinking of red wine.  Filled with plentiful polyphenols, it is resveratrol that stands in the spotlight as it and its metabolites provide the antioxidant and HDL stimulating potential supporting a heart healthy lifestyle.*

What if a glass of wine a day was equivalent to the recommended daily intake of baby aspirin or statins prescribed by a doctor?  What if a glass of wine demonstrated protective effects against not only cardiovascular conditions, but also protected the cerebral vascular system, in other words, potential protection from stroke?   Initial studies more than a decade ago, demonstrated the first evidence of partial neuroprotective action of chronic administration of resveratrol in vivo, suggesting a possible model for neurodegenerative injury (Virgili M et al., 2000).  Five years later, subsequent studies showed pre-infused resveratrol protected the spinal cord from ischemic reperfusion injury in vivo by which resveratrol was found to decrease oxidative stress and increased nitric oxide release (Kiziltepe et al 2004).  Further investigation led to findings that it not only acted as an antioxidant, but also directly inhibited voltage-gated K+ channels, which have been implicated in neuronal apoptosis (cell death) supporting another possible mechanism of action (Gao ZB et al., 2005, 2006).  Indeed, resveratrol has been noted for its potential pre-dose protection, but recent studies also demonstrated post-ischemic dose immediately after traumatic brain injury reduced oxidative stress and lesion volume, which could be explained by its ability to relax smooth muscle in the wall of basilar artery contributing yet another role as a vasodilator (Ates O et al., 2007, Karaoglan A et al 2008).*

Resveratrol’s beneficial effects include: (1) antioxidation (free radical scavenger and modulation of neuronal energy homeostasis and glutamatergic receptors/ion channels, (2) vasodilatory effects in pre- and post-treatment infusion protection of ischemic reperfusion injury, (3) directly increases sirtuin 1 (SIRT 1) activity and NAD (+) related to increased lifespan in various species similar to calorie restriction, and (4) pretreatment protection against cerebral ischemia and other organ systems, which could be a great potential target for further studies in treatment modalities.*

More recently, an additional mechanism which resveratrol was suggested to have included anti-inflammatory characteristics as well.  Zhang and team explained both in vitro and in vivo studies highlighting inhibition of activated microglia (2010).  In doing so, microglia are unable to release pro-inflammatory factors, which produced reactive oxygen species, and activated signal pathways leading to neuroinflammation.  With that being said, Parkinson’s disease (PD) and many other neurodegenerative diseases arise from over active microglia-mediated inflammation.  As a subsequent follow-up study, Zhang and team applied resveratrol in vivo primary midbrain neuron-glia cultures that demonstrated clear protection of neurotransmitters (in the case of PD – dopamine) against LPS-induced neurotoxicity through the inhibition of microglial activation.  In addition to these findings, Johns Hopkins University Anesthesiology and Critical Care Medicine team revisited resveratrol’s effect on stroke, demonstrating in vivo resveratrol pretreatment dose dependently protected against the ischemic reperfusion stroke model.  Heme oxygenase was selectively deleted to suggest a potential intracellular pathway by which resveratrol can provide cell/organ resistance against neuropathological conditions (2010).*

Indeed further studies are in order to determine specific dose and timing of resveratrol for optimal neuroprotective effects, but what is certain is that moderate consumption of resveratrol does demonstrate neuroprotective effects.  As you air, swirl, and sip that dark red tonight and experience its dynamic nature in flavor and consistency, also realize its vast effect on your overall health.  Cheers to the heart, cheers to the brain, cheers to deep reds <cling, cling>.

References (For an extended list please contact us)

Sakata Y et al., “Resveratrol protects against experimental stroke: putative neuroprotective role of heme oxygenase 1,” Exp Neurol, 2010; 224, 325-9.

Zhang F et al., “Anti-inflammatory activities of resveratrol in the brain: role of resveratrol in microglial activation,” Eur J Pharmacol, 2010; 636:1-7.

Zhang F et al., “Resveratrol protects dopamine neurons against lipopolysaccharide-induced neurotoxicity through its anti-inflammatory actions,” Mol Pharmacol, 2010; 78:466-77

*These statements have not been evaluated by the Food and Drug Administration.  This product is not intended to diagnose, treat, cure or prevent any disease.

Author’s bio: Dr. Anh Thu V. Tran is the Medical Director & Nutrition Consultant for Cyvex Nutrition, PGY-1 Resident with  UC Davis Family Medicine Residency Network, and Founder of Strive to Live Well.  She holds a M.D. from St. George’s University, a M.S. in Nutrition from Loma Linda University, and a B.Sc. in Biology & Women’s Studies from UC Irvine.

**By Anh Thu V. Tran, MS, MD – Medical Director & Nutrition Consultant, Cyvex Nutrition**

As the #1 global cause of death at 29% of all causes, an estimated  1 out of 3 American adults, equating to ~81 million, have at least one or more forms of Cardiovascular Disease (CVD) (American Heart Association CDC-DHDSP, WHO 2010 updates).  With technological advances being more effective and less invasive, along with having a more concrete understanding of such conditions, why do we still fall behind in preventing such numbers?

Indeed the answer is not simple.  What is certain, however, is that there are major elements that we can control against CVD.  Namely, diet, physical activity, and mental health are major players.  Consumption of polyphenol-rich diets alone has been associated with a reduced risk of cardiovascular disease, particularly foods and beverages with high oligomeric procyanidins (OPC) and flavonoids (such as anthocyanidins).

Yet again the spotlight shines on the ever so tiny and delicate, yet packed with heart-healthy benefits: berries.  Their unique composition of carbohydrates counterbalanced by organic acids (citric, malic, phenolic acids) and enzymes (polyphenolic substrates such as phenolic acids & flavonoids), high solubility of cell wall components (pectin, cellulose, and hemicellulose), rich in pigments (anthocyanins, carotenoids, and other polyphenols), vitamins and minerals are universally recognized to accentuate their sweet flavor, enticing aroma, and healthy benefits.

From reds to blues to purple and even blackberries,  berries are rich sources of essential nutrients and phytochemicals demonstrated epidemiologically and clinically.  Heart healthy diets that include a variety of berries improve cardiovascular performance or activity in both healthy subjects and those with underlying and preexisting conditions.

High density lipoprotein cholesterol (HDL) is the “good” cholesterol that works against cholesteryl ester transfer protein (CETP) in its facilitation of low-density-lipoprotein (LDL) and triglycerides (“bad” cholesterol and blood fat respectively).  The latter being the culprit to cardiovascular insults.  In a recent single-blinded, randomized, placebo-controlled intervention trial, middle aged healthy and un-medicated subjects consumed a moderate amount of berries against a control product.  Moderate consumption demonstrated favorable modulation in platelet function, HDL-cholesterol and blood pressure.  Of all the nutritional biomarkers, it was that of vitamin C and polyphenols in berries that made the most impact (Erlund I et al., 2008).  Clinical correlations as such were also found in those with poor cardiovascular profiles.

In a double-blind, randomized, placebo-controlled trial of dyslipidemic adults, participants consumed either 160gm berry-derived anthocyanin supplements versus a placebo.  There was a statistically significant increase of HDL-cholesterol and decrease in mass and activity of plasma CETP, decreasing insults from LDL-cholesterol and triglycerides (p<0.001) (Qin et al 2009).  The proposed mechanisms of actions are as follows: (1) Upregulation of endothelial nitric oxide synthase, (2) decreased activities of carbohydrate digestive enzymes & oxidative stress, and (3) inhibition of inflammatory gene expression and foam cell formation.

Served fresh, juiced, freeze-dried and/or as purified extract such as anthocyanins, anyway you like it – the blackberry, black currant, blueberry, cranberry, escobillo, lingonberry, strawberry to name a few not only nourish the taste buds, but also the heart.

References:

Basy A et al, “Berries: Emerging impact on cardiovascular health,” Nutr Rev, 2010; 68:168-77

Erlund I et al., “Favorable effects of berry consumption on platelet function, blood pressure, and HDL cholesterol,” Am J Clin Nutr, 2008; 87:323-31.

Seeram Np, “Recent trends and advances in berry health benefits research,” J Agric Food Chem, 2010; 58:3869-70

Qin Y et al., “Anthocyanin supplementation improves serum LDL- and HDL-cholesterol concentrations associated with the inhibition of cholesteryl ester transfer protein in dyslipidemic subjects,” Am J Clin Nutr, 2009; 90:485-492.

Author’s bio: Dr. Anh Thu V. Tran is the Medical Director & Nutrition Consultant for Cyvex Nutrition, PGY-1 Resident with  UC Davis Family Medicine Residency Network, and Founder of Strive to Live Well.  She holds a M.D. from St. George’s University, a M.S. in Nutrition from Loma Linda University, and a B.Sc. in Biology & Women’s Studies from UC Irvine.

**Post written by guest writer Anh Thu Tran, MS, MD**

With an estimated 8.3 million out-patient doctors visits and 500,000 hospital stays each year equating to an increasing medical cost of $500 million associated with urinary tract infections (UTIs), it is no wonder that suggestive scientific claims of amelioration of this condition can be found naturally in a distinctly tart, sweet, and voluptuously vibrant red fruit, the cranberry.  It has made its mark as quite a powerhouse of natural goodness¹.

UTIs are common among women, but men have a significant increase in susceptibility as they age (~13 million versus 2 million, respectively) ².  Those with diabetes mellitus or other immune compromising conditions, enlarged prostates, kidney stones, or any obstruction of the urinary tract also have a higher susceptibility.  Affecting a wide range in demographics and a full-spectrum of clinical consequences of such condition, the cranberry presents a feasible, cost effective, and tasty adjunct to current prevention and management of UTIs.

The cranberry’s richness in polyphenols and antioxidant potential has raised this little fruit to fame in the past decade³.  More targeted studies have demonstrated that the acidity and polyphenolic profile (that of flavonoid composition: anthocyanidins, proanthocyanidins, cyanidins, and quercetins) have contributed to the suggested primary mechanism of action against bacterial growth and attachment to the lining of the urinary tract (such as Type I and P-fimbriated uropathogenic: Escherichia Coli) ⁴.  With that being said, the spotlight should also be pointed to a close family-member of the cranberry, The Lingonberry.

Lingonberry (Vaccinium vitis-idaea) is a small, red, edible berry and is related to the cranberry and blueberry family, the Ericaceae.  They are similar, but not as tart as cranberry and commonly consumed as jam, jelly, juices, sauce, wine, liqueur, and/or syrups.  They contain plentiful organic acids, vitamin C, beta carotene, vitamins B1, B2, and B3, and potassium, calcium, magnesium, and phosphorus.  However, compared to the cranberry, the lingonberry is found to have similar or possibly better effect against UTIs due to a polyphenolic profile that is twice as high in antioxidant potential and total polyphenols.  One hundred milligrams of anthocyanins can be found in 3.5ounces of fresh ligonberries^5-7.  Extension of such potential should undergo more clinical review, but for now, lingonberries offer an additional approach against UTIs and if anything, should be acknowledged for its antioxidant power!

Cyvex Nutrition’s Lingonol™ Lingonberry extract contains a minimum of total antioxidant value of 4500micromole TE/g and 25% of which is from polyphenols (anthocyanins, proanthocyanidins, and other flavonoids).

References

1. Litwin MS and Saigal CS., “Urologic Diseases in America.” DHHS, PHS, NIH, NIDDK. NIH publication (2007)

2. Griebling TL., “Urinary tract infection in women, Urologic Diseases in America.”  DHHS, PHS, NIH, NIDDK. NIH publication (2007)

3. Jepson RG and Craig JC., “Cranberries for preventing urinary tract infection.”  Cochrane database Syst Rev (2008)

4. Guay DR., “Cranberry and urinary infection.”  Drugs (2009)

5. Ek S et al., “Characterization of phenolic compounds from Lingonberry (Vaccinium vitis-idaea).”  J Agric Food Chem (2006)

6. Zheng Wei et al., Oxygen radical absorbing capacity of phenolics in blueberries, cranberries, chokeberries, and lingonberries.”  J Agric Food Chem (2003)

7. Kuhau, “The flavonoids: A class of semi-essential food components: their role in human nutrition.”  World Rev of Nutr and Diet (1976)

Author’s bio: Dr. Anh Thu Tran is the Nutrition Consultant and Research & Development Coordinator at Cyvex Nutrition.  She holds a M.D. from St. George’s University, a M.S. in Nutrition from Loma Linda University, a B.Sc. in Biology & Women’s Studies from UC Irvine, and will work under the UC Davis Family Residency Network 2010.