Category Archives: Fish oil

Rheumatoid Arthritis

Rheumatoid Arthritis Awareness Week: The Benefits of Fish Oil

Rheumatoid Arthritis and the Benefits of Fish Oil

June 13th marks the beginning of Rheumatoid Arthritis Awareness Week, a campaign run by the National Rheumatoid Arthritis Society. One of the main goals of the campaign is to heighten awareness of the early warning symptoms of this condition, and to support those who have been recently diagnosed.

Many people do not recognise the early warning signs of rheumatoid arthritis. This is because the symptoms can be blamed on ‘overdoing things’. By recognising the three key symptoms – swelling, stiffness and fatigue – sufferers can take early action to seek help and find the right treatment. Because the disease is progressive, if sufferers are able to recognise and address the condition early, they are more likely to find treatment effective.

What is Rheumatoid Arthritis?

Rheumatoid arthritis is an autoimmune disease. Normally the body’s immune system produces an inflammatory response as part of the healing process. If a joint is injured, special chemicals are released that cause short-term pain and swelling, immobilising the joint to give it opportunity to heal. However, sometimes this process can go awry and the immune system creates long-term chronic, painful inflammation that damages the joint tissues.

How is it Treated?

Medications for rheumatoid arthritis tend to work by suppressing inflammation. Examples are corticosteroids, non-steroidal anti-inflammatory drugs (NSAIDs) and disease-modifying anti-inflammatory drugs (DMARDs).

However, recent studies have also highlighted the success of natural agents in modifying the inflammatory response. One of the most promising natural supplements linked to treatment of rheumatoid arthritis is fish oil.

The Benefits of Fish Oil

A study published just last year tested the effects of fish oil versus placebo on 144 patients with recent onset rheumatoid arthritis. Most of the patients were women in their 50s, and were already taking conventional arthritis medication. The group was given either placebo capsules or supplements of high-dose fish oil (5.5g per day).

Those taking the fish oil showed greater improvement in daily function in the first three months. After a year, the women given the high dose fish oil showed double the rate of remission compared with those on placebo.

It makes sense that fish oil should relieve inflammatory diseases such as rheumatoid arthritis. Fish oil is a rich source of the omega-3 fatty acids, EPA and DHA. The body uses both omega-3 and omega-6 fatty acids to make chemicals called prostaglandins and leukotrienes. The right balance of these chemicals help to control inflammation, and EPA and DHA promote the anti-inflammatory chemicals.

These omega-3 fatty acids actually have a similar action to medications used in rheumatoid arthritis: they help to block production of several inflammatory chemicals involved in arthritis, including prostaglandin E2 and leukotriene B4, and peptide mediators, tumor necrosis factor (TNF)α and IL-1β (2).

Plant foods such as flaxseed and hempseed are sources are a type of omega-3 fat called ALA. However, the long chain omega-3 fats used in this study are only found in fish and seafood, such as salmon, herring and mackerel, and in algal oil which represents a vegan source.

The study authors concluded that fish oil led to ‘increased rates of remission and decreased drug use’ in those with recent onset rheumatoid arthritis. This study certainly indicates that fish oil supplementation would be a sensible supplement to consider for anyone recently diagnosed with rheumatoid arthritis.

References
1. Proudman Sm et al (2015) Fish oil in recent onset rheumatoid arthritis: a randomised, double-blind controlled trial within algorithm-based drug use. Ann Rheum Dis 2015;74:89-95
2. Proudman SM et al (2008) Dietary omega-3 fats for treatment of inflammatory joint disease: efficacy and utility. Rheum Dis Clin North Am. 34:469–79.

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Vegans respond well to algae-based omega-3 supplements

Omega-3 levels in vegans are low and can successfully be addressed with algae-based omega-3 supplements according to a new study (1).

The study of 165 vegans found that their omega-3 index was just 3.7%, which is too low and indicates a raised risk for heart disease.

The ‘omega-3 index’ is a measure of omega-3 in cell membranes. A level below 4% represents a high risk of developing heart disease, while a level of above 8% is considered low risk (2).

A selection of the group were supplemented with 243mg of algae-derived EPA + DHA each day for four months. During this time, the omega-3 index of this group rose from 3.1% to 4.8%. The researchers concluded that “low dose supplementation with algae-sourced DHA and EPA may mitigate the potential adverse effects of deficiency in this population.”

The recommended intake of omega-3 is 450mg per day, according to the government’s Scientific Advisory Committee on Nutrition. Unfortunately in the UK the average intake is around half this amount, at just 250mg per day.

Incidentally, the level of omega-3 found in vegans in this study is actually no lower than that found in omnivores. This population-wide deficiency in omega-3 is a concern, especially considering the range of health benefits linked with this particular fat. In addition to its cardio-protective benefits, omega-3 has been linked with eye health, brain health and a healthy immune system.

An important consideration for those wanting to boost their omega-3 intake is the danger of toxins. The richest source of omega-3 is oily fish, but unfortunately these fish have a tendency to accumulate mercury and other toxic pollutants such as dioxins and PCBs. For this reason, women who are pregnant or breastfeeding are advised not to eat more than two servings of oily fish each week.

fish_oil
Omega-3 levels in vegans are low and can successfully be addressed with algae-based omega-3

Because mercury tends to accumulate in protein rather than fat, fish oil supplements can provide a ‘cleaner’ way to obtain your daily omega-3. For this reason, supplements do not pose the same concerns over mercury ingestion as oily fish in the diet.

Dioxins and PCBs are rather a different story. These contaminants tend to accumulate in fat, and so are present not only in oily fish, but also in poor quality fish oil and algae-based supplements. For this reason it is essential to choose a very good-quality supplement. For example, Eskimo-3 was found to contain the lowest levels of dioxins and PCBs in independent testing. Products from Biocare and Higher Nature also performed well. To illustrate the variability in quality, the same study found that the level of contaminants in Boots Cod Liver Oil was more than 50 times greater than that found in Eskimo-3. Dioxin levels in Tesco’s Cod Liver Oil were also well above the maximum limit for fish oils intended for human consumption (3).

Good quality vegan supplements represent a clean way of supporting omega-3 levels, as algae can quite easily be grown in controlled, unpolluted conditions. This is the case for supplements such as opti3, which is made from algae grown in a fully-controlled pharmaceutical facility. This particular supplement is therefore recommended for pregnant and breastfeeding women owing to its clean profile.

In light of the above study results, vegans wanting to ensure healthy levels of omega-3 would certainly do well to consider such a supplement. Even those of us who aren’t vegan or vegetarian might consider algae-based supplements as a sustainable and pure source of omega-3.

References

1. Sarter B et al (2014) Blood docosahaenoic acid and eicosapentaenoic acid in vegans: Association with age and gender and effects of an algal-derived omega-3 fatty acid supplement. Clinical Nutrition. March 2014.

2. Harris WS (2008) The omega-3 index as a risk factor for coronary heart disease. American Journal of Clinical Nutrition 87: 6 1997S-2002S

3. FSAI (2002) Dioxins, Furans and PCBs in Farmed and Wild Salmon, Farmed Trout and Fish Oil Capsules. http://www.fsai.ie

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Movember: Eat to Beat Prostate Cancer

Thousands of men across the UK are sprouting moustaches this month, in aid of Movember, an annual event aimed at raising awareness of men’s health issues.

Men are less likely to visit their GP when ill, less likely to access disease screening services and less likely to seek support with healthy-living initiatives such as stop smoking schemes. Consequently, serious diseases such as cancer and diabetes tend to be diagnosed later in men than in women. This is why raising awareness and encouraging a dialogue about men’s health issues is particularly important.

Prostate cancer is a particular focus for the Movember campaign because this disease can be difficult to spot in its early stages. In addition, one in eight men in the UK will develop prostate cancer, making this the most common type of cancer in men.

Lamberts_fish_oil
For those who do not eat oily fish regularly, it may be prudent to supplement with a good quality fish oil supplement.

The prostate, found only in men, is located below the bladder. Its function is to produce fluid to nourish and protect semen. The prostate often enlarges as men get older, causing troublesome symptoms for some men.

Symptoms of all prostate problems include:

  • needing to urinate often, especially at night
  • difficulty starting to urinate
  • straining to urinate or taking a long time to finish
  • pain when urinating or during sex

There is plenty of research suggesting that dietary changes help reduce the risk of developing prostate cancer.

Studies have found that men with a higher level of omega-3 fatty acids in their body had a reduced risk of prostate cancer. Omega-3 is present in oily fish and in smaller amounts in flaxseed and some plant foods. One study of more than 6000 men found that men who regularly ate oily fish such as salmon, sardines and mackerel had a reduced risk of developing this condition. The men who ate no fish were more than twice as likely to develop prostate cancer as those who ate moderate to high amounts. For those who do not eat oily fish regularly, it may be prudent to supplement with a good quality fish oil supplement.

High dairy consumption is linked to an increase risk of prostate cancer as evidenced by a number of studies in this area. One study found that men who consume two and a half serving of dairy each day have a 40 per cent increase in prostate cancer risk (2). This is probably because eating diary raises levels of Insulin like Growth-like Growth Factor which can promote growth of cancer cells. A recent meta analysis reports that soya consumption, on the other hand, is linked with a reduced risk of prostate cancer (3), and so replacing cow’s milk with soya milk is likely to be a helpful measure.

Cancer is known to be triggered by damaging molecules known as free radicals. Antioxidants ‘mop up’ these free radicals and so it seems sensible to ensure that the diet is abundant in rich sources of these nutrients. Men who eat four servings of vegetables a day have a 35 per cent reduced risk of prostate cancer compared to those who eat just two servings. In addition, vegetarian men have a lower risk of developing prostate cancer than meat eaters.

Two supplements that have been widely studied in relation to prostate cancer risk are selenium and saw palmetto. Selenium has antioxidant properties and aids DNA repair, and a recent meta-analysis showed a potential inverse association between toenail, serum, and plasma selenium levels and prostate cancer risk (4). Selenium is present in most multi-vitamin and mineral supplements. Alternatively, just two Brazil nuts each day will fulfil your daily requirement of this mineral.

Saw palmetto is often used for its protective benefits. This nutrient is anti-inflammatory and also helps to prevent the conversion of testosterone to DHT, an agent that promotes prostate cancer (5). Large studies have found saw palmetto supplementation to be beneficial in benign prostatic hyperplasia (BHP) or non-cancerous enlargement of the prostate (6). While more research need to be done in this area, saw palmetto appears to be safe to supplement and has no known drug interactions, making it a worthy of consideration in supporting prostate health.

References

1. P Terry et al, Fatty fish consumption and risk of prostate cancer, The Lancet (2001), vol 357 (9270), pp 1764-1766

2. Chan JM, Stampfer MJ, Ma J, Ajani U, Gaziano JM, Giovannucci E. Dairy products, calcium, and prostate cancer risk in the Physicians’ Health Study. Presentation, American Association for Cancer Research, San Francisco, April 2000.

3. Hwang YW, Kim SY, Jee SH, et al.: Soy food consumption and risk of prostate cancer: a meta-analysis of observational studies. Nutr Cancer 61 (5): 598-606, 2009

4. Brinkman M, Reulen RC, Kellen E, Buntinx F, Zeegers MP. Are men with low selenium levels at increased risk of prostate cancer? Eur J Cancer 2006;42:2463-71.

5. W H Goldmann et al, ‘Saw palmetto berry extract inhibits cell growth and Cox-2 expression in prostatic cancer cells’, Cell Biology International (2001), vol 25(11), pp 1117-24.

6. Wilt TJ, Ishani A, Rutks I, MacDonald R. Phytotherapy for benign prostatic hyperplasia. Public Health Nutr. 2000 Dec;3(4A):459-72.

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Fish Oil Supplements

We are often told that we should eat oily fish or take a fish oil supplement, but why? When? Which one do you choose?

Why do you need fish oil?

Although maligned by the weight loss industry, dietary fats exist for a reason. They are present in plant and animal tissue because they perform vital functions for those organisms and, when we consume them, they do the same for us. The body needs to ingest or synthesise a ready supply to maintain health. Some lipids are even essential because they cannot be manufactured by the body and must be obtained through diet. There are many different forms of lipids, one of the most crucial subsets are the essential fatty acids (EFAs), omega-3 and omega-6.

Some anthropologists believe consumption of omega-3 fats lead to profound changes in the human brain. We probably evolved on a 1:1 ratio of omega 3:6 in our diets (1). Post agricultural and industrial revolutions, this has dramatically switched in favour of omega-6 and is now closer to 16:1. Balancing omega-3 and 6 fats is crucial for the management of many chronic diseases. Oils from cold water fish such as salmon, sardines, trout and mackerel have been the subject of thousands of research papers, showing efficacy for a number of conditions. They provide a rich source of the active omega-3 fats, eicosapentanoic acid (EPA) and docosahexaenoic acid (DHA). Vegetarian sources of omega-3 require further conversion in order to metabolise EPA and DHA.

The most obvious way to tackle the shortfall in dietary omega-3 is to consume more oily fish. Individual taste is often a barrier. Furthermore, the beneficial long chain omega-3 fats can be damaged by cooking and the larger fish such as salmon can contain high levels of heavy metals and other contaminants. Therefore fish oil supplementation presents a practical way to increase omega-3 intake, but not all fish oil products are created equally.

When choosing a product it is important to be sure that it has been produced with due regard to environmental impact, has an exemplary quality profile and is effective.

How much do you need?
The omega-3 essential fats, EPA and DHA, are mostly found in oily fish such as sardines and anchovies

To maintain healthy levels of essential fats, the government recommends that we all eat at least two portions of oily fish each week but this can be difficult to achieve through diet alone, especially if you don’t like to eat fish! A good quality fish oil supplement can be a great option to ensure levels are high enough to maintain good health.

How do you know if a supplement is good quality?

Here are a few tips when looking for a good quality fish oil supplement:

  • Look for a fish oil supplement that is produced from small fish such as anchovies and sardines as the levels of essential fats within these fish are naturally more concentrated. You will therefore get better quality oil.
  • Look at where the fish are sourced. Small fish sourced from areas such as the clear pacific waters will drastically minimise the level of pollutants. This will mean you will get cleaner, more pure oil.
  • Look for oil that has had minimal processing. Fatty acids are delicate and can become damaged when put through aggressive production methods. If minimal heat and chemicals are used, the oil will be closer to its natural form.
  • Look for variety. If fish oil is pure and clean, then it can be made into capsules and liquids that have very little fishy aftertaste. Some fish oils can even be mixed with fruit bases so that adults and children can enjoy taking a daily supplement.

References:

1. Simopoulos AP Evolutionary aspects of diet, the omega 6/omega 3 ratio and genetic variation: nutritional implications for chronic diseases. Biomedicine and Pharmacotherapy 60 (2006) 502-507.

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The role of omega-3 in heart health

Deaths caused by cardiovascular disease are generally premature and could easily, in some cases, be prevented by making lifestyle changes that include adopting a healthy lifestyle and increasing physical activity.

The role of lipid lowering (cholesterol and triglyceride) in reducing the risk of mortality and morbidity from cardiovascular disease is well documented. The cardiovascular benefits of omega-3, certainly in terms of cholesterol and triglyceride management, are probably the most researched of all the dietary nutrients known to influence cardiovascular disease risk. With the recent approval of the use of pure eicosapentaenoic acid (EPA) as a prescription treatment for hypertriglyceridemia [1] and with overwhelming evidence for EPA’s role over docosahexaenoic acid (DHA) in cholesterol management, [2] consumers should be aware of the differential effects of the two main omega-3s, EPA and DHA, on cardiovascular disease risk factors and why they should choose isolated EPA over generic fish oil.

EPA and lipid management

Whilst fish oil provides a convenient dietary intervention for maintaining heart health, the differential effects of the two main long-chain omega-3s, eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) on cardiovascular disease risk factors means that not all fish oil products are equal in their action.

Firstly, generic oils generally contain around 30% total omega-3 and are therefore not considered viable as a therapeutic. For example, the optimal triglyceride-lowering doses of omega-3 are 3-4g/day, with little evidence to support lipid-altering efficacy in doses of less than 1g/day. [3] In addition to providing a soluble means for transporting cholesterol and triglycerides through the blood, lipoproteins have cell-targeting signals that direct the lipids they carry to certain tissues.

Pharmepa Step 1: Restore (E-EPA 90) contains the purest ethyl-EPA concentrate available without prescription

Whilst high density lipoproteins (HDL) correlate with better health outcomes, effectively clearing cholesterol from the system, low density lipoproteins (LDL) are, in contrast, considered the cholesterol ‘bad boy’ and are responsible for the detrimental effects associated with total cholesterol.

Both EPA and DHA decrease triglyceride levels, and whilst EPA lowers LDL levels, DHA appears to increase LDL levels [4, 5]. Given that products that contain a mixture of EPA and DHA may increase LDL levels, the benefits of a pure EPA product understandably extend to both cholesterol and triglyceride management. Indeed, the cholesterol-lowering ability of pure EPA at a dose of 1.8 grams in a study of approximately 19,000 statin-treated patients with hypercholesterolaemia was shown to reduce the 5-year cumulative risk of major coronary events by 19%. Igennus’ Pharmepa Step 1: Restore (E-EPA 90) contains the purest ethyl-EPA concentrate available (90%) without prescription, delivers 1g pure EPA in just two easy-to-swallow capsules, and is ideal for those individuals wanting to manage cholesterol and triglyceride levels.

AA to EPA ratio and cardiovascular health

In addition to altering lipid metabolism, omega-3 may also improve cardiovascular health by inhibiting inflammatory products derived from the key pro-inflammatory fatty acid arachidonic acid (AA). AA and EPA are converted through phospholipase A2, cyclooxygenase (COX) and lipooxygenase (LOX) to prostaglandins, thromboxanes and leukotrienes, as well as various hydroxyl-fatty acids, and the AA to EPA ratio provides an established risk factor for numerous inflammatory-related conditions, including poor cardiovascular health. Indeed, inflammation is an important process in the development of cardiovascular disease; chronic inflammation, characterised by elevated plasma levels of inflammatory markers such as C-reactive protein (CRP) and IL-6, are commonly found in subjects at high cardiovascular risk, including type2 diabetics and patients with coronary heart disease. [6] Supplementing with EPA, in addition to triglyceride and cholesterol improvement, increases EPA blood levels, improves the AA to EPA ratio (which directly correlates with changes in improved LDL levels) and reduces cardiovascular related inflammation. [7]

In summary, EPA, unlike DHA, lowers levels of triglyceride, lowers ‘bad’ cholesterol and increases ‘good’ cholesterol, whilst reducing inflammation via management of the AA to EPA ratio. By providing pure isolated EPA at the concentrations required for therapeutic outcomes, Igennus’ Pharmepa range of EPA products are ideal health supplements for managing optimal heart health by managing lipid levels and modulating dysregulated inflammation. The prescription-strength ethyl-EPA Pharmepa Restore & MaintainTM  protocol is an innovative two-step treatment programme formulated to re-establish a healthy inflammatory status within the body. Step 1 counteracts an unhealthy AA to EPA ratio – the direct measure of inflammatory status, and step 2 ensures long-term balance for optimal cardiovascular health benefits.

References

1.  Ballantyne CM, Braeckman RA, Soni PN: Icosapent ethyl for the treatment of hypertriglyceridemia. Expert opinion on pharmacotherapy 2013, 14:1409-1416.

2. Yokoyama M, Origasa H, Matsuzaki M, Matsuzawa Y, Saito Y, Ishikawa Y, Oikawa S, Sasaki J, Hishida H, Itakura H, et al: Effects of eicosapentaenoic acid on major coronary events in hypercholesterolaemic patients (JELIS): a randomised open-label, blinded endpoint analysis. Lancet 2007, 369:1090-1098.

3. Pirillo A, Catapano AL: Omega-3 polyunsaturated fatty acids in the treatment of hypertriglyceridaemia. International journal of cardiology 2013.

4. Itakura H, Yokoyama M, Matsuzaki M, Saito Y, Origasa H, Ishikawa Y, Oikawa S, Sasaki J, Hishida H, Kita T, et al: The change in low-density lipoprotein cholesterol concentration is positively related to plasma docosahexaenoic acid but not eicosapentaenoic acid. Journal of atherosclerosis and thrombosis 2012, 19:673-679.

5. Cottin SC, Sanders TA, Hall WL: The differential effects of EPA and DHA on cardiovascular risk factors. The Proceedings of the Nutrition Society 2011, 70:215-231.

6. Brevetti G, Giugliano G, Brevetti L, Hiatt WR: Inflammation in peripheral artery disease. Circulation 2010, 122:1862-1875.

7. Tani S, Nagao K, Matsumoto M, Hirayama A: Highly Purified Eicosapentaenoic Acid May Increase Low-Density Lipoprotein Particle Size by Improving Triglyceride Metabolism in Patients With Hypertriglyceridemia. Circulation journal : official journal of the Japanese Circulation Society 2013.

 

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Raynaud’s Awareness Month

February is Raynaud’s Awareness Month, a campaign aimed at increasing understanding of this debilitating condition amongst the general public. Many sufferers of Raynaud’s are unaware that their condition has a name and do not know that there are therapies available to help.

Raynaud’s Phemomenon (RP) affects somewhere between 3-20% of the population worldwide, with women more commoly affected than men. Raynaud’s is characterised by problems with blood flow to the extremities, causing pain, tingling sensations, numbness or discomfort. These symptoms are most often present in the hands, but can also occur in the toes, ears and nose. During a Raynaud’s episode, the fingers will turn white as blood supply is interrupted. They may then turn blue before blood flow resumes, accompanied by a feeling of burning. Episodes can be triggered by emotional stress or by temperature changes.

Ginkgo Biloba may help combat Reynaud's Disease
Ginkgo has been reported to improve circulation in small blood vessels

There is currently no documented cure for Raynaud’s. However, studies suggest that some nutritional supplements may be useful in relieving symptoms.

The herb ginkgo has been reported to improve the circulation in small blood vessels and reduce pain in people with Raynaud’s disease. In a recent double blind study, Ginkgo supplementation taken over a 10-week period reduced the number of attacks experienced by Raynaud’s sufferers (1).

Essential fatty acids are also reported to be beneficial for those with Raynaud’s. Fish oil has a number of effects that may improve blood circulation. It reduces vascular reactivity and blood viscosity, suggesting that it should help improve blood flow and circulation in Raynaud’s patients. A double-blind study did in fact find that fish oil supplementation improved tolerance to cold and delayed the onset of symptoms. Other studies have found fish oil to be useful in decreasing both frequency and severity of attacks (2). Evening primrose oil has similar vascular effects to that of fish oil, and a small double blind study found it offered similar benefits in Raynaud’s (3).

A form of Vitamin B3 known as inositol hexaniacinate, reduces spasms in the arteries and improves peripheral circulation. For this reason it has been tested as a therapy for Raynaud’s and in larger doses has been found to improve circulation and reduce attacks (4,5). Larger doses of 3-4 grams, like those used in the studies, should only be taken under the supervision of a medical practitioner.

Problems with magnesium metabolism may also factor in Raynaud’s (6). Magnesium deficiency can cause blood vessels to spasm. Ensuring an optimal intake of this mineral helps blood vessels to ‘relax’ and encourages healthy blood flow. The recommended daily intake of magnesium is 300mg for men and 270mg for women, but many adults in the UK fall short. Increasing intake of green, leafy vegetables, nuts, seeds and pulses can boost magnesium levels significantly.

Finally, dietary and lifestyle changes can also help to manage this condition. Smoking, which constricts blood vessels, will aggravate Raynaud’s and so giving up the cigarettes should improve symptoms immensely. Relaxation techniques and stress management are also recommended. Other helpful dietary measures include cutting down caffeine and alcohol, and reducing fatty and fried foods.

If you’d like more information on Raynaud’s you can visit the Raynaud’s & Scleroderma Association website which is dedicated to helping those affected by the condition.

References

1. Muir AH, Robb R, McLaren M, Daly F, Belch JJ (2002) The use of Ginkgo biloba in Raynaud’s disease: a double-blind placebo-controlled trial. Vasc. Med 7(4):265-7.

2. DiGiacomo RA et al. (1989) Fish-oil dietary supplementation in patients with Raynaud’s phenomenon: a double-blind, controlled, prospective study. Am J Med 68:158–64.

3. Belch JJ, Shaw B, O’Dowd A, et al. (1985) Evening primrose oil (Efamol) in the treatment of Raynaud’s phenomenon: a double-blind study. Thromb Haemost. 54:490-494.

4. Holti G (1979) An experimentally controlled evaluation of the effect of inositol nicotinate upon the digital blood flow in patients with Raynaud’s phenomenon. J Int Med Res 7:473–83.

5. Ring EF, Bacon PA. (1977) Quantitative thermographic assessment of inositol nicotinate therapy in Raynaud’s phenomenon. J Int Med Res. 5:217–22.

6. Leppert J, Aberg H, Levin K, et al. (1994) The concentration of magnesium in erythrocytes in female patients with primary Raynaud’s phenomenon; fluctuation with the time of year. Angiology 45:283–8.

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