**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 and Nutrition Consultant, Cyvex Nutrition

From getting kids off to school and getting to work, attending board meetings, making soccer practices and dance recitals, we are all in constant motion.  Unfortunately, most of us are strapped for time and find it difficult to stay fluid with the current as we fall behind in meeting nutritional needs or wish to reach optimal health by consuming nutrition to meet daily requirements.  Either way, as we become more knowledgeable of how effective a balanced and/or optimal diet is to our health, the demand for a quick and easy solution to keep up with our lifestyles is a must.  The “do-it-yourself” mentality influenced by the recession has produced wellness-focused consumers.  From low-calorie/low-sugar, sugar-free, naturally-sweetened, and all natural, functional beverages are the new black, as lifestyle consumers are wearing the latest creations from the inside out.

With an annual expected growth rate of 6.1 percent from 2007 to 2012, the United States has the largest functional food and beverage market in the world worth almost $700 billion in 2008.  In 2009 alone, U.S. sales of functional foods and beverages reached almost $40 billion, up 2.7% from previous year with $21.6 billion from beverages, making it the largest functional segment.  Traditional beverage companies have expanded their products by adding functional ingredients and/or introducing functional products to their line.  Functional drinks among dieters and/or weight lifters have always been around, but it is the new trend of optimizing time and nutrition in a bottle that drives this market forward.  Recent studies demonstrate consumers are more likely to purchase a product that claims health versus nutrition benefits (Verbeke W et al., 2009).  Scientific evidence and crafty formulations help consumers readily accept new ingredients as well as the more popular ones which owe their success to appropriate delivery and clear communication of health benefits.

In response, functional beverages are tailored towards specific gender, age, and body type/weight.  The safety, optimal doses, interactions, and long-term benefits have more research necessary to be determined, but many of the added ingredients have been linked to some science-based health claims.  As consumers become more health conscience, the demand and market value for health promoting products will continue to increase as should more focused research behind these products to determine the mechanism of action to optimize their formulations.  A recent study comparing 3,100 foods, beverages, spices, herbs, and supplements of total antioxidant content demonstrates the start of such work to further elucidate the health benefits of antioxidants (Carlsen MH et al., 2010).  However, more research in this direction is a must to keep up with the market.  From a metabolic, antioxidant, alertness/cognitive, immune, digestive boost and anti-aging potential to replacing the routine multivitamins supplements, functional beverages as a segment is keeping up with the current by aiming to aid health as well as quench thirst.

References:

Carlsen MH et al., “The total antioxidant content of more than 3,100 foods, beverages, spices, herbs, and supplements used worldwide,” Nutr J; 2010, 9:3.

Verbeke W et al., “Consumer appeal of nutrition and health claims in three existing product concepts,” Appetite; 2009, 52:684-92.

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

The growing segment of active sixty-five years and over Americans not only denotes successful commitment for research towards extension of lifespans, but also the acknowledgment that it really does not mean much if you can live longer, if you can’t enjoy it.  The key emphasis is longevity, however in light of extended lifespans and improved longevity is the expected eventual overdrive the body must undergo to maintain some state of homeostasis – the efforts to stay balanced in the aging process.

Of the many protectors of our body – the basic immune response to disturbances, such as infection and trauma, involves Inflammation.  However, it is also this process that can easily speed out of control against our bodies either in the natural progression of aging or accelerated destruction of disease and other pathological processes.  It is obvious this double-edged sword walks the fine line as we age.  What’s promising is that adopting a healthier lifestyle that includes adequate rest, daily physical exercise, specific diets, and halting poor choices (e.g. tobacco smoking) proactively work against such acceleration.

We previously discussed how flavonoids are effective even at a young age (Holt EM., et al 2009).  High consumption of fruits and vegetables reduce markers related to inflammation and oxidative stress among adolescents; this is supported on a molecular level and can be applicable to the immune process at any age and in associated disease processes.*  The Agricultural Research Service (ARS) of the University of California, Davis, has conducted numerous studies in the past decade demonstrating how inflammation favors the risk of cancer and chronic diseases such as Cardiovascular Disease (hypertension and dyslipidemia) and Diabetes Mellitus Type II (insulin resistance).  Dr. Daniel H. Hwang and team, after exhausting filtering of numerous phytochemicals, has finally placed the spotlight yet again on flavonoids in their role against certain inflammatory triggers (TMK-1 kinase and IRF1 dimerization and phosphorylation).  Luteolin among the 6 other phytochemicals most effectively targets these enzymes in its cascade of biochemical signaling that lead to the formation of gene products known to trigger inflammation (Lee JK et al 2009).*  Luteolin, found in food such as celery, green peppers, chamomile tea, and thyme, demonstrated to be the most effective of all other flavonoids studied (quercetin, chrysin, eriodicytol, hesperetin, and naringenin).

In addition, recent data suggests a promising role for luteolin as a possible candidate in developing immune-modulatory and neuroprotective agents on central nervous system (brain and spinal cord) against a specific trigger: the microglia.  The microglia has been confirmed as a major culprit in age-related disease progression.  Although protective, it also takes on that double-edged detriment.  The Institute of Human Genetics, University of Regensburg investigation showed inhibitory effects of luteolin on pro-inflammatory cytokine expression in microglia.  With the identification of several novel luteolin-regulated genes, their findings provide a molecular basis to understand the versatile effects of luteolin on microglial homeostasis (Dirscherl K., et al 2010).*

In the uncertainties of life – certainty does exist.  Making effective lifestyle choices are within your control and although not necessarily capable of halting the double-edged sword, but at least taming as such by the choices we make, including which fruits and vegetables we consume,  is the best we can do to help prevent diseases and slow-down the progression of aging.

References:

Holt EM., et al., “Fruit and vegetable consumption and its relation to markers of inflammation and oxidative stress in adolescents,” J Am Diet Assoc, 2009; 109:414-21.

Lee JK., et al., “Suppression of the TRIP-dependent signaling pathway of Toll-like receptors by luteolin,” Biochem Pharmacol, 2009; 77:1391-400.

Dirscherl K., et al., “Luetolin triggers global changes in the microglial transciptome leading to a unique anti-inflammatory and neuroprotective phenotype,” J Neuroinflammation, 2010; 14:7-3.

*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 and Nutrition Consultant,  Cyvex Nutrition

Sunscreen use increases as July and August months bring on the warmer weather for t-shirts, tank tops, shorts, skirts, and bikinis.  Unbeknownst to many of us, protection from sun exposure is important all year round and should not be limited to poolsides, beaches, hiking trails, or other outdoor wonders of warmer months.  Cloudiness and hazy days do not protect us from the UV rays, but rather reach our bodies as if it were actually a bright and sunny day.  3.5 million cases in two million people are diagnosed annually with skin cancer in the United States and the incidence is more than the combined incidences of cancers of the breast, prostate, lung and colon (American Cancer Society, 2009, Skin Cancer Foundation 2010).

The current CDC recommendations against UV sun-damage is as follows: (1) use of sunscreen of sun protective factor (SPF) 15 or higher with UVA and UVB protection, (2) wear protective clothing, (3) wear protective hat to shade face, head, ears, and neck, (4) wear sunglasses with UV block , and (5) seek shade especially during midday hours (2010).  UVA is related to skin aging and UVB is associated with skin cancer.    The reality is that the warmer months are spent underneath the sun, with minimal clothing at peak UV exposure from 10AM to 4PM, and most people actually enjoy seeking out the sun rather than shade, which emphasizes the importance of and dependency on sunscreen.  However, what if there was an additional protective factor?  What if this factor were to work on defending you against UV radiation from the inside and outside of your body?  What if this product could be applied as in topical creams/lotions and also as an option one could add as a side to a lunch or dinner plate. Among the top superfoods (for good reason), this green vegetable, resembling a tree, filled with  rich vitamins, minerals, fiber, and plentiful phytochemicals has been suggested in the protection and repair of UV sun damage to the skin.*  It is no surprise this superfood spotlight shines on broccoli (yet again).

Recent in vivo studies demonstrated 25 percent less skin tumors following chronic UV exposure for 17 weeks when  fed broccoli extract for 13 weeks than compared to standard protective agents on hairless animal model at Johns Hopkins University.  In addition, tumors that were developed were 70% smaller in diameter and depth (Dinkova-Kostova AT, et al. 2010).  Replication of this animal model to confirm such protection is in the works with subsequent anticipated clinical studies to follow. Dinkova-Kostova and team demonstrated that exposure to UV accompanied with sulforaphane glucosinolates (SGS) also provided the validity behind selection of sprouts over mature broccoli (2010).  Previous in vivo studies using both animal and human skin demonstrated immediate cellular defenses resulting from UVR-induced inflammation and edema in mice and reduction in susceptibility to erythema (redness) arising from narrow-band 311 nm UVR in humans, presenting potential in topical application of cruciferous extracts (Talalay P, et al. 2007).*  Optimizing products for broccoli sprout applications in supplements, functional foods, and/or topical products would be advantageous in providing the greatest potential of effectiveness and uniqueness to products.

What are the actives within broccoli and other cruciferous vegetables (cauliflower, cabbage, and Brussels sprouts) that provide such protection?  Beyond the already known nutritious richness, these vegetables also have high levels of a group of phytochemicals called glucosinolates, which are further metabolized by the body into isothiocyanates.  Phenythyl isothiocyanates (PEITC) and sulforaphane have also been applied as adjunct therapy in chemotherapy in halting the proliferation of tumor cells.  Sulforaphane is the main metabolite and has been associated with mobilizing cellular defenses against UV damage.  Its precursor, glucoraphanin (sulforaphane glucosinolates – SGS) at optimized levels can be found in the sprouts of broccoli compared to the mature vegetable.  Eating your vegetables, yet again, holds weight in a healthier diet.  So next time someone asks if you would like a side of broccoli, remember, you are not only getting a side of vegetables with a punch of rich nutrients, but also a side of sun protection!

References:

Dinkova-Kostova AT et al., “Dietary glucoraphanin-rich broccoli sprout extracts protect against UV radiation-induced skin carcinogenesis in SKH-1 hairless mice,” Photochem Photobiol Sci, 2010; 9: 597-600

Talalay P et al., “Sulforaphane mobilizes cellular defenses that protect skin against damage by UV radiation,” PNAS, 2007; 104:17500-17505

*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.