Cardiovascular protective role of resveratrol: dietary sources and supplementation

Cardiovascular protective role of resveratrol: dietary sources and supplementation by Anamaria Cucliciu

Resveratrol is a naturally occurring polyphenol with phytoestrogenic properties. Resveratrol is widely present in plants which reproduce from seeds[1] and is found in high concentrations in grape skin. Other rich sources include red wine, peanuts, pistachios, dark chocolate, bilberries, mulberries, blueberries and cranberries.[2]

Resveratrol is thought to have various protective functions in humans, including antioxidant, anti-inflammatory, cardioprotective, antiviral, antiproliferative and anti-carcinogenic [1]. The ‘French paradox’ indicates that despite the high fat diet and smoking habits of the French population, the country has very low mortality and morbidity rates from coronary heart diseases. This epidemiological phenomenon has been attributed to their moderate consumption of red wine. Subsequently, it was questioned weather this cardioprotective action is due to resveratrol alone or other polyphenols and phytochemical substances also play an important role.

The growing base of evidence for the health-protective effects of resveratrol gave rise to the interest in resveratrol supplementation. But is this nutraceutical actually efficient?

Following oral administration, resveratrol is rapidly and efficiently absorbed. However, it has a poor bioavailability because of the rapid and extensive hepatic first pass-metabolism.[3]

It has been established that resveratrol’s beneficial effects on health are produced in a dose-dependent manner.[2] A large number of cell culture and animal studies[1],[2] have showed that mechanisms behind resveratrol’s cardioprotective role include:

  • defence against ischemic-reperfusion injury
  • vasorelaxation
  • protection and maintenance of intact endotheliumreduction of vascular inflammation
  • suppression of low density lipoprotein oxidation
  • antiatherosclerotic properties
  • inhibition of platelet aggregation
  • regulation of energy metabolism
  • estrogenic  activity

However, the molecular mechanisms behind these properties are complex and not well defined. Most human studies have been done on a small scale and have yielded mixed results, their findings not always fitting with in vitro and experimental models data.[1],[2],[3]

Although resveratrol is almost certain to have a protective effect on human health, including the cardiovascular system, further large scale clinical studies are needed to evaluate resveratrol’s supplementation efficacy, pharmacokinetics, adequate doses, tolerability and potential interaction with other drugs.[2] Consuming resveratrol rich foods is surely beneficial to health, while it is yet to be established whether supplementation can be recommended for cardiovascular disease prevention and perhaps even treatment.

Anamaria is a Nutrition and Dietetics student at King’s College London, highly interested in nutrition research and cardiovascular health, yet passionate about badminton and dance, infatuated with cats and peanut butter.



1. Hao, HD and He, LR (2004) Review. Mechanisms of Cardiovascular Protection by Resveratrol. Journal of Medicinal Food 7 (3) 2004, 290-298. doi:10.1089/jmf.2004.7.290

2. Bukarica, LG, Protić, D, Kanjuh, V, Heinle, H, Novakovi, R, Šćepanovi, R (2013) Cardiovascular effects of resveratrol. Vojnosanit Pregl ; 70(12): 1145–1150. DOI: 10.2298/VSP120613012G

3. Sahebkar, A (2013) Effects of resveratrol supplementation on plasma lipids: a systematic review and meta-analysis of randomized controlled trials. Nutrition Reviews , 71(12):822–835. DOI: 10.1111/nure.12081

Posted in Nutrition, Supplements

Is Fructose Making Us Fat?

Is Fructose Making Us Fat? by Syrone Burr

The increase in obesity has become more pronounced in recent decades. The reason for this increase is often attributed to basic energy imbalance i.e. we are eating more calories than we are burning off through activity, and this may be true for many of us, but could there be more to it than that? Are all calories really equal? Well the answer to the question, really depends on its interpretation. From a metabolic perspective, many researchers studying carbohydrate metabolism, in particular the metabolism of fructose, believe the answer may be no.

Obesity studies in the USA have found significant correlation between increases in the intake of High Fructose Corn Syrup (HFCS) and the rise in obesity.  HFCS was introduced into the US food supply in 1970 as a cheaper and sweeter substitute to sucrose, and its use increased one hundred fold between 1970 and 1990 and currently represents 40 percent of all caloric sweeteners. This increase far exceeds changes in intake of any other food or food group and also happened to precede the rapid increase in the prevalence of obesity. For this reason many researchers have been interested in the potential link between increased HFCS consumption and the epidemic of obesity.

What’s so bad about fructose?

Fructose is a naturally occurring sugar found in fruits, vegetables and honey and has been part of the human diet for hundreds of years. HFCS is produced by enzymatic isomerization and contains both glucose and fructose. So how is the fructose found in HFCS different from fructose naturally found in food?  The answer is that there is no difference. The fructose is the same whether it is found naturally or is produced industrially by enzymatic isomerization, however the concern with HFCS is in part due to the sheer volume that has been introduced to food products and the fact that it is so pervasive that it can be difficult to find food products in which it is not contained.

Fructose metabolism and satiety

Glucose and fructose are metabolized in very different ways, with fructose mainly being metabolized in the liver. Of particular concern is the fact that fructose is able to bypass the main regulatory step in glycolysis, facilitated by the enzyme phosphofructokinase, and in doing so effectively ‘forces’ glycolysis, resulting in de novo lipogenesis.

Fructose also does not stimulate the release of insulin, which acts in the body as a satiety signal to the brain, releasing hormones into the circulation, which inhibits further food intake. Insulin is also instrumental in the release of leptin, a long-term regulator of food intake. Leptin feedback to the hypothalamus, signals available energy stores, while low leptin feedback signals starvation. Without insulin, and without leptin the brain believes the body to be starving and not only fails to release a satiety signal in response to the fructose intake but instead sends out hunger signals causing an increased intake of calories.

So is fructose making us fat? Research suggests that a diet high in fructose could, not only increase the amount of fat synthesized in the body but could also cause overconsumption.  Further research is needed but until then, if you are concerned about overweight it may be wise to reduce your consumption of added sugars and sugar sweetened beverages. Eating a healthy and balanced diet in conjunction with regular exercise will help to establish and maintain a healthy weight.

Syrone Burr is a year 2 BSc Nutrition and Dietetics student interested in the role of nutritional factors in managing chronic illness, in particular the condition cystic fibrosis and I am a (volunteer) dietetics research assistant at Royal Hampshire County Hospital.

Posted in Added Sugar, Fructose, Lipids and Lipid Metabolism

Thinking of supplementing with calcium and scared of cardiovascular disease?

Thinking of supplementing with calcium and scared of cardiovascular disease? by Humaira Rehan

Osteoporosis is a skeletal disorder in which bones become thinner, brittle, and more susceptible to fractures.  Although Osteoporosis affects both men and women, post-menopausal women account for 80% of all cases for osteoporosis. Oestrogen in the body plays an important role in preventing bone loss, and this protection declines sharply after menopause.

Bone tissue is not inert but dynamic in nature. It serves as a repository for vital minerals including calcium phosphate. Resorption of calcium from bones and its deposition back to the bones (bone remodelling) plays an important role in calcium homeostasis within the body.

Here comes the important bit: calcium cannot be made by the body. We need to get calcium from our diet. Not having enough calcium can adversely affect bones. Usually calcium supplements are given to people over 65 as a standard to prevent or treat Osteoporosis. It’s recommended to take 1200mg of calcium every day.

Recently there has been controversy surrounding the calcium supplements and its association with cardiovascular disease (BMJ. 2010 Jul 29; 341:c3691. doi: 10.1136/bmj.c3691). This created an intense interest because of the widespread use of calcium supplements. Other studies raised similar concerns (BMJ. 2010 Jul 29; 341:c3691. doi: 10.1136/bmj.c3691).

However, a number of studies – including RCTs (randomised clinical trial), show no significant increases in cardiovascular effects connected to calcium supplements (Journal of Bone and Mineral Research, Vol. 26, No. 1, January 2011, pp 35–41). Meta-analysis of data from other studies also showed intake of calcium to reduce the risk of clinical fractures without raising any concerns of high cardiovascular risks.

In the absence of any conclusive evidence it would not be wise to stop prescribing calcium supplements until independent confirmation from other RCTs is observed. But in all of the studies it was seen that elderly and institutionalised population with low intake of calcium, patients on glucocorticoid, and patients with osteoporosis, benefited from high doses of calcium (1200mg-1500mg per day).

Calcium is not only important for bone health, it is very important for a myriad of functions in the body. It’s essential in cell signalling, blood clotting, muscle contraction and nerve functions. It’s essential for a number of vital processes in the body. New research has linked calcium to being a factor in reducing obesity, colorectal cancer and hypertension. But a lot more research is needed in these areas.

Its best to get calcium from diet and most of the people eating a varied diet will have enough calcium intakes.  Dairy is a very good source of absorbable calcium. Calcium is also present in green leafy vegetables, tofu, okra, almonds and fish like sardines and pilchards. However, if you feel that your dietary intake is not sufficient and you take a calcium supplement, just be wary of the fact that very high doses of calcium from supplements (> 2500mg/day) can cause calcification in soft tissues, disturbances of GI tract, and kidney stones.

Additional References:

Role of Calcium in the Body’s Nutrition by Arielle Kamps, Demand Media at

High Calcium Intake Linked to Heart Disease, Death by M. Bridget and M. S. J. Kuehn

Role of oestrogen in the development of osteoporosis by T. C. Hillard and J. C. Stevenson

Humaira Rehan is a year 2 BSc Nutrition and Dietetics student at King’s College London.

Posted in Education, Nutrition, Supplements

Gluten free – The magic diet bullet? Some food for thought…

Gluten free – The magic diet bullet? Some food for thought…

by guest blog author Rebecca Haskoll


Not so long ago, ‘gluten’ was a word reserved for science books, bakers and those with coeliac disease (CD). CD is an autoimmune reaction to gliadins (the soluble fraction of gluten), which results in damage to the small intestine causing nutrient malabsorption. Symptoms of CD include diarrhoea, anaemia, fatigue and sometimes an intensely itchy rash called dermatitis herpetiformis. There is no drug treatment or cure for CD, just adoption of a gluten free diet (GFD) for life.

Gluten is in a LOT of foods – not just the obvious ones such as bread and pasta, but also in flavourings, soups, sauces, beer and even chocolate bars – so coeliacs must find GF substitutes.

Five years ago, most of those substitutes were only available on prescription. Then came the ‘Free From revolution’. Genius was the first company to commercialise GF bread. Supermarkets began to market their own ‘Free From’ ranges. Suddenly whole aisles were dedicated to living GF. Recent research indicates that 16.5% of the UK population now regularly buys GF products.

But how did this happen? After all, the prevalence of CD in the UK is estimated only to be 0.8-1.9%. Although NICE suggests that as many as 1 in 100 people may have CD, many will remain asymptomatic and presumably won’t adopt a GFD.  Non-coeliac gluten sensitivity (NCGS) has an estimated prevalence of 6-10%. NCGS seems to overlap with irritable bowel syndrome and there is a question over whether symptoms are caused by gluten proteins or byfermentable carbohydrates. Nevertheless, this population is likely to choose GF foods.
The only other proven reason for someone to adopt a GFD is wheat allergy. So what else could account for the rise in ‘gluten free living’?

Consider these…
Celebrities seem to love a GFD. Everything from Miley Cyrus’s tweets to Gwyneth Paltrow’s cookbooks and tennis supremo Novak Djokovic’s diet plans have exclaimed that going GF has positive health effects. Gwyneth’s mental clarity improved. Miley lost weight. Novak won Grand Slams. What have the rest of us got to lose? More on that later…

Bestselling diet books such as Grain Brain by American neurologist Dr David Perlmutter have received extensive coverage in the popular press. Dr Perlmutter believes the consumption of carbohydrates and gluten causes neurological manifestations (everything from headaches to Alzheimer’s) probably in ALL humans.

In a recent interview, Dr Perlmutter cites several papers. On further reading, their authors are not quite as adamant about the ‘all humans’ part of his theory: Hadjivassiliou et al. (also here) hypothesise that patients with CD-like blood-test results who continue to consume gluten may develop neurological dysfunction. Fasano discusses the possibility that gluten-induced protein expression implicated in ‘leaky guts’ may also cause blood-brain-barrier permeability (it is not conclusive that this protein causes a critical level of gut permeability in non-coeliacs). Both authors acknowledge that large cohort studies are needed.

So you don’t have CD but decide a GFD is for you… The everyday realities are that avoiding gluten is really quite difficult and GF foods are expensive. But are there potentially more serious consequences to going GF than just being out of pocket? Coeliacs on strict GFDs have been shown to have lower intakes of some micronutrients and lower fibre intakes than the general population. This may be because GF staples such as breads are less likely to be fortified than their wheat-based counterparts or because many GF foods – particularly baked goods – do not have the best texture, so are abandoned in favour of other foods that may lack the nutrients found in glutinous grains. If you don’t need it, is it worth the sacrifices?

Gluten free the magic diet bullet? I’m not so sure…

Becky is a student dietitian at King’s College London, interested in role of nutritional factors in managing chronic illness.

Posted in Education, Gut Health, Healthy Eating, Nutrition, Uncategorized

“The E. coli made me do it.” – Bacteria and Behaviour

“The E. coli made me do it.”  – Bacteria and Behaviour by guest blog author Katsiaryna Dalidovich.

In a recent The New Yorker article, James T. Rosenbaum – Professor of Ophthalmology, Medicine, and Cell Biology at Oregon Health and Science University – reviewed the research suggesting that E. coli and other bacteria may cause depression, anxiety, and other mental illnesses in humans, by altering our brain chemistry. This really makes you wonder, ‘Just how much influence do our microbes have on us?’

A lot has changed since DNA structure was first described in 1953. At that time our genes were regarded as our biological destiny. We now realize that human genes are outnumbered 150-fold by the non-human genes in and on our bodies. These belong to the collection of bacteria, viruses, fungi, and other microbes that share our bodies, and outnumbering our own cells ten to one.

Exploration of all the metabolic intermediates in human metabolism is not yet complete. So where do we start our search for the contribution of the ‘foreign’ metabolites produced by our inner ecosystem? What is their role in human health and illness?

In 2008, the first stage of the Human Microbiome Project pioneered research on human microbial species. The project resulted in a vast number of findings. One of the most interesting suggested that gut bacteria may alter our brain chemistry affecting our moods and behaviour.

Bacteroides fragilis and autism

Autism is a complex spectrum of neurodevelopmental disorders with classic features:
— impaired communication
— poor social engagement
— repetitive behaviour

Interestingly, autistic children are over 3.5 times more likely to experience GI problems.

Trying to investigate the “tummy problems”, Arizona State University scientists found that autistic participants had greatly reduced diversity of gut bacteria. So what is the role of gut bacteria in autism?

Researchers at Caltech conducted research on mice models of autism. The pups went on to develop “leaky gut,” — a condition often seen in autistic children. On analysis, scientists found that the blood of autistic mice contained 46 times more 4EPS, than that of the control group (4EPS is a molecule produced by an as yet unidentified strain of gut bacteria). What is more, injecting healthy mice with 4EPS made them more anxious. A similar molecule has been found at elevated levels in autistic patients.

A second finding revealed that “autistic” mice had lower levels of Bacteroides fragilis in their guts compared to the control group. Additionally, after feeding them with B. fragilis, their behaviour and gastrointestinal health both improved.

Gut microbiota and behavioral phenotype

Steve Collins and his group at McMaster University have done studies where they have shown that transplanting the microbiota from an animal with an anxious phenotype into a germ-free animal gives that animal an anxious phenotype; and likewise, transplanting the microbiota of an animal with a depressive phenotype into a germ-free animal renders that animal depressive.

Gut–Brain Axis Pathways

There are a number of ways our gut bacteria communicate with our brain. The Caltech researchers demonstrated an endocrine pathway, in which involved metabolites from gut bacteria leak into blood and reach our brain affecting its function. The McMaster University researchers speculated that the changes they observed were mediated by gut bacteria indirectly influencing metabolism of their human host’s neuroactive chemicals and their precursors. Other recent research has suggested many more possible pathways by which our gut microbiota communicate with our brain.

Could the microbes that inhabit our guts help explain that old idea of “gut feelings?”

There is a lot of pre-clinical data generated from animal models of depression, anxiety and other behavioural disorders. Researchers identified that certain strains of bacteria or certain psychobiotics are effective in treatments of those pathologies. However, a number of questions have to be answered before clinical trials can take place. These are:

  • Does our microbiome cause these diseases?
  • Is treatment that works in animal models safe for human?
  • What are the proposed effects of such treatments?
  • Are the microbes initiating or just propagating the disease?
  • Are the treatments necessary, sufficient, or neither?

Katsiaryna is a year 2 BSc Nutrition student at King’s College London with an interest in nutrigenomics, gut microbes and human health.

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Posted in Education, Gut Health

Lipid and Lipoprotein Metabolism – Short Presentations

This set of short presentations covers part of my main lectures on lipid and lipoprotein metabolism.  Each short video covers a particular  aspect of lipid transport through the body using the analogy of a factory and product delivery system.  These slides accompany the lecture material for Metabolism (5BBB0223) but would be useful as a lipid and lipoprotein review for the MSc Nutrition students (7MNT0004-Principles of Nutrition), Intercalated BSc Nutrition Medical Students (6MNTNP00 – Principles of Nutrition) and Year 3 Nutrition and Dietetics students (6MNT0302 – Applied Nutrition).  Suggestions for additional topics/posts welcome.

Video Presentation Topics:

  1. What are lipoproteins?
  2. What is the exogenous lipid transport?
  3. What is the endogenous lipid transport?
  4. What is the reverse cholesterol transport pathway?
  5. How do the lipid transport pathways relate to each other?
  6. How are lipids released from adipose and used as metabolic fuel in other tissues? 
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Posted in Lipids and Lipid Metabolism, Nutrition

Introduction to Dietary Fats – Classification, Digestion and Absorption

I have recorded and posted the following three presentations to provide a refresher/summary on dietary fats.  These are targeted towards the year 2 Metabolism students (5BBB0223) who have taken my Lipids and Lipoproteins lectures but may be useful to the year 1 Introduction to Nutrition Students (4MNT0102) or anyone needing a short summary of the classification of dietary lipids and the digestion and absorption of dietary lipids.  Comments welcome for additional topics to record and post.


Dietary Fats – Classification, Digestion and Absorption (Part 1a)

Dietary Fats – Classification, Digestion and Absorption (Part 1b)

Dietary Fats – Classification, Digestion and Absorption (Part 2)

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Posted in Lipids and Lipid Metabolism, Nutrition
Dr Scott Harding

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