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Intermittent Claudication: Modulation With Anti-Inflammatory Nutrition

by David Seaman, DC, MS, DABCN

As with coronary artery disease, also called cardiovascular disease (CVD), peripheral vascular disease (PVD) is caused by a progressive atherosclerotic process.

Over time, systemic atherosclerosis leads to the progressive occlusion of the distal aorta and iliac arteries, which can lead to symptoms such as intermittent claudication. About 40 percent of patients with PVD suffer with intermittent claudication. While PVD does not always produce symptoms, severe PVD may lead to gangrene. PVD patients may also manifest pain at rest. Not surprisingly, the functional impairment of patients with PVD is considered in the context of pain-free walking distance.

There is a direct relationship between PVD and CVD. There is a 90 percent chance that those with PVD will develop CVD. Risk factors of PVD are similar to those for coronary artery disease: age (>40), cigarette smoking, diabetes, hyperlipidemia, hypertension, and hyperhomocysteinemia. We should be aware that most of these risk factors are not associated with symptoms; that is, their influence on the atherosclerotic process occurs without symptoms. Only when a critical threshold (atherosclerosis-induced ischemia) is reached do the symptoms of intermittent claudication appear.


"A recent analysis of heart-healthy foods suggested that it is possible to reduce the expression of heart disease by more than 75 percent."

Study Design

A recent article described a research trial (randomized, double-blind, controlled) involving a nutritional intervention for patients suffering with intermittent claudication due to PVD. A total of 60 patients, who claudicated at a walking distance of less than 200 yards, were assigned to two groups and studied for 12 months. Subjects in each group were counseled on how to implement a Mediterranean-style diet; subjects were urged to increase their intake of fruit, vegetables, legumes, and fish, and to avoid fast foods and precooked meals. Subjects in each group were also given an antiplatelet medication (triflusal) and a hemorrheologic agent (pentoxifylline). Each group was asked to walk for an hour per day.

In addition to the above, each group consumed a 500 ml dairy product. The control group received regular semi-skimmed milk; the supplemental group received a fortified dairy product (skim milk fortified with vitamins A, B6, D, E, and folic acid, as well as oleic acid [an omega-9 fatty acid], and the omega-3 fatty acids eicosapentaenoic acid [EPA] and docosahexaenoic acid [DHA]).

Outcomes

Both groups exhibited improvements in pain-free walking distance, which was attributed to the lifestyle changes and the Mediterranean diet. The control group improved by 44 meters, while the supplemental group improved by 280 meters, which the authors described as "outstanding" and due to the anti-inflammatory supplementation.

Various inflammatory markers, such as adhesion molecules, C-reactive protein, plasminogen activator inhibitor, and free radical activity, were assessed in both groups at baseline, 6, and 12 months. No significant differences were noted in these markers.

Hyperhomocysteinemia is considered to be an independent risk factor for PVD, as elevated levels of homocysteine seem to promote coagulation and reduce vasorelaxation, thereby potentiating ischemia. At baseline, eight members of the supplemented group and nine controls had hyperhomocysteinemia. At 12 months, the controls still had hyperhomocysteinemia, while the homocysteine levels in the supplemented group were lowered to the upper end of normal.

The most significant anti-inflammatory change involved plasma levels of EPA and DHA, and the ratio of arachidonic acid (omega-6) to EPA (omega-3). Arachidonic acid (AA) is the precursor to many pro-inflammatory autocoids, such as prostaglandin E2, thromboxane A2, and leukotriene B4. In contrast, EPA is the precursor the anti-inflammatory varieties of these autocoids, those being prostaglandin E3, thromboxane A3, and leukotriene B5. DHA is the precursor to anti-inflammatory autocoids referred to as resolvins and docosatrienes. The authors suggest that an improved ratio of omega-6 to omega-3 fatty acids may reduce autocoid-driven inflammation and improve vasoperfusion, which would lead to a lessening of intermittent claudication and improved pain-free walking distances. The ratio of AA:EPA in the supplemented group was 8.95:1 at baseline and improved to 5.9:1 at the end of 12 months. In contrast, the control group began at a 9.69:1 ratio and ended at a 10.02:1 ratio of AA to EPA.

Summary and Practical Applications

Peripheral vascular disease, like cardiovascular disease, is characterized as an inflammatory response of the respective arteries. Not surprisingly, anti-inflammatory agents such as aspirin have been used to treat each condition.

The enriched dairy product used in this trial contained only 200 mg of EPA and 130 mg of DHA, which amounts to about one standard fish oil capsule per day. The 330 total milligrams of EPA/DHA represents about one-third the level that is typically recommended in the clinical setting. In other words, it is possible that more substantial improvements can be realized in patients with IC.

In my experience, moderate anti-inflammatory nutritional efforts yield moderate results. The more devoted a patient is at consuming anti-inflammatory foods and taking anti-inflammatory supplements, the better his or her clinical outcomes.

A recent analysis of heart-healthy foods suggested that it is possible to reduce the expression of heart disease by more than 75 percent. The following foods make up the polymeal: fish, wine, dark chocolate, fruit and vegetables, garlic, and almonds. All foods are to be consumed daily, save for fish, which is supposed to be consumed four times per week.

Readers should consider that the polymeal approach to eating is likely to be beneficial for all diseases promoted by inflammation. In addition to the foods listed in the polymeal, wild game, grass-fed animals, and omega-3 eggs are good additions that are very similar to fish in their health benefits. Red potatoes and sweet potatoes are also anti-inflammatory. Meals should be spiced to taste - try Italian, Greek, and Indian spices; they are anti-inflammatory and taste better compared to salt and pepper.

Several supplements can be taken to help reduce inflammation, including a multivitamin/mineral, magnesium (400-1,000 mg/d), EPA/DHA (1-3 g/d), coenzyme Q10 (100 mg/d), lipoic acid (400 mg/d), acetyl-L-carnitine (1,000 mg/d), garlic (5 mg allicin/d), and an anti-inflammatory botanical containing ginger, turmeric, and boswellia. Only patients on strong anticoagulants need to have concerns about such recommendations; however, it is wise to check for potential drug-nutrient interactions for patients on medications.

The clinical perspective we should have regarding such dietary changes and supplementation is straight-forward: The goal is to reduce a chronic inflammatory that we all suffer from to varying degrees. If we are fortunate, the outcome will be reduced inflammation and reduced disease expression, as was demonstrated in the patients with intermittent claudication.


References

  1. Carrero JJ, Lopez-Huertas E, Salmeron LM, Baro L, Ros E. Daily supplementation with (n-3) PUFAs, oleic acid, folic acid, and vitamins B-6 and E increases pain-free walking distance and improves risk factors in men with peripheral vascular disease. J Nutr 2005;135:1393-99.
  2. Franco OH, Bonneux L, de Laet C, et al. The polymeal: a more natural, safer, and probably tastier (than the polypill) strategy to reduce cardiovascular disease by more than 75%. Brit Med J 2004;329:1447-50.
  3. Seaman DR. Nutritional Considerations in the Treatment of Soft Tissue Injuries. In: Hammer WI (editor). Functional Soft Tissue Examination and Treatment by Manual Methods, 3rd ed. Boston: Jones and Bartlett (in press for 2005).
  4. Seaman DR. Nutritional Considerations for Rehabilitation and Health Promotion. In: Liebenson CL (editor). Rehabilitation of the Spine: A Practitioner's Manual. Baltimore: Williams & Wilkins (in press for 2005).
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