Strawberry Supplements Impact on Blood Lipidic Parameters Essay (Critical Writing)

Introduction

Atherogenesis is a major cause of mortality and morbidity from Coronary Heart Disease (CHD), particularly in the Western World. In hyperlipidemic patients, low-density lipoproteins (LDL’s) responsible for transport of cholesterol and triglycerides in vascular system undergo macrophage- and endothelial cell-mediated oxidative modifications. Modified LDL tends to aggregate in arterial wall, and is taken up by macrophages, which in turn converts to foam cells (Aviram & Fuhrman 1998, pp. S45-S50).

These produce plaques in the arterial wall and blocks blood flow. Effective diets that reduce blood lipid, especially LDL levels, and more importantly prevent oxidative modification, are useful in prevention of CHD. Dietary supplements which contain mono-saturated fatty acids and poly-phenols, and are rich in vitamin C and E have anti-oxidant property. Epidemiological studies revealed that these may prevent CDH events. In this paper (Jenkins et al. 2008, pp.1636-1644) authors have tested strawberries as against oat bran bread as source of anti-oxidants in the patients already on lipid-lowering diet. The purpose was to examine whether strawberry supplement can affect the various blood lipidic parameters and can attenuate LDL oxidation.

A larger implication was to evaluate the efficacy of such diets in prevention of atherogenesis. In my opinion, despite profound relevance of the subject, the paper suffers from some weakness in objectivity, methodology and interpretation of the results.

Body

Authors have tested the hypothesis that ellagic acid and anthocyanins, anti-oxidant ingredients of strawberry, effectively alleviate the oxidative damage of already lowered LDL in hyperlipidemic patients. From a background of low-lipid diet, mostly comprising high fiber, plant sterols and low animal fat (for at least 1 year), 30 randomized subjects of both sexes were divided in strawberry group, with added strawberry in the diet, and oat bran group, fed on extra bran on equal calorific value. Before the tests (the sub-study baseline), and during strawberry/bran study in Phase 1 (4-wk), complete blood parameters including lipid profile, oxidative indices in serum LDL fraction (TBRS and conjugated dienes) and protein, and systolic and diastolic blood pressure were periodically recorded.

After Phase 1, the diet supplements in the two groups were exchanged following a “wash-out” period of 2-wk (exclusively on low-lipid diet), and were then fed on the replacement diets for another 4-wk (Phase 2). The recorded values were statistically treated for mean and ±SD, and test of significance at given P values was carried out between, a) baseline and strawberry group and b) between strawberry and bran groups. The significant finding was that while LDL oxidation was inhibited in strawberry group, it did not happen in the bran group. However, both diet supplements almost equally prevented protein oxidation.

The palatability of strawberry was significantly higher than oat bran. The cholesterol lowering effect of low-lipid diet given for 1-year was not significantly influenced by strawberry/bran added to such diet. In Phase 1 and 2, most of the other blood parameters remained unchanged as compared to the baseline values. The authors concluded that added strawberry has lowered LDL oxidative damage.

The context of the paper is highly relevant in current times as many cholesterol reducing drugs, e.g. Statins, Clofibrate, Torcaprib pose several side-effects, and many patients refuse such treatments. Also, unfortunately, addition of anti-oxidant vitamins viz. C and E in the diet also has not proven to lower the incidences of CDH, rather they actually increased the problem (Fisher, Lees & Spence 2006, pp. 2431-2432). Consequently, the importance of dietary reduction of cholesterol and serum lipid oxidation has gained such proportion that this issue was discussed in an editorial of a reputed journal (Jenkins, Kendall & Marchie 2005, pp. 793-795).

There are limited randomized controlled studies on such diets in LDL oxidation abatement, and present paper is one of them. The anti-oxidant property of strawberry was attributed to only two compounds, but phytochemical analysis of strawberry revealed besides phenolic compounds, presence of other anti-oxidants like folate and vitamin C (Seeram 2007, pp. 5-8). Further, like other anti-oxidants, polyphenol bioavailability is said to be poor as they occur in glycosylated conjugated forms, and are not readily absorbed in intestine. It is not necessarily true that consuming excess of berries would enrich blood with anti-oxidants.

In the experimental design the patients were kept on cholesterol-lowering diet for prolong periods but still the cholesterol level were above normal, hence the subjects for strawberry study continued to be hyperlipidemic. Most likely, it was assumed that strawberry supplementation would further lower LDL-C content, but actually it did not happen. Subjects fed on higher oat bran were taken as controls and those on strawberries were treated as experimental.

It was assumed that having equal calorie would be enough to negate the effects other than that of the anti-oxidants. Oat bran is high fibrous supplement and has LDL-C lowering effect. Besides, as this factor was used as denominator for calculating conjugated dienes and TBARS as indicators of LDL anti-oxidation properties of supplements, such controls would give erroneous data. Both groups should be considered as experimental (treated), and a separate negative control group fed only on lipid-lowering diet during the test period should have been included. Two-way ANOVA with student’s t– test would have been appropriate to analyze significant difference in three groups.

Further, there should have been an additional group (positive control) being fed on oat bran and dried powdered strawberry pulp. This would have provided the anti-oxidants with additional beneficial effect of bran. Authors have not mentioned the logic of alternating the diet supplements to the two groups. Possibly a longer period of same diet supplementation per group with some “wash out” intervals would have given better results.

Authors have also used non-parametric data (palatability and satiety tests) but how significance tests were performed is not given. As pointed out by Horgan (2001, pp. 141-144), full statistical details should have been appended in the paper. The calculations used for high LDL-C has limitations, and modification of Friedewald’s formula as adopted by Sniderman et al. (2003, pp. 495-504) should have been used. TBARS measurements in serum LDL fraction may encounter interferences of other oxidative products. As this is a vital data, an improvised method could have been employed in which TBARS is separated from serum by HPLC and measured spectrofluorimetrically (Walter et al. 2004, p. 1997).

The finding that strawberry is more palatable than excess oat bran was projected as the prominent result, whereas it was based on only the qualitative data set. Surprisingly, >1 year cholesterol lowering diet did not markedly lower the LDL-C

(-11.6%). Unlike what authors have perceived, it appears that the participants were not following the dietary chart. The data in Table 1 and 3 (column 1, 4) are repetitive. Instead, profiles of 86 original participants and of sub-study baseline would have given comparative account of before and after 1-year of cholesterol lowering diet. Table 2, though is relevant from nutrition point of view, has not much relevance in present context and just mentioning that NCEP guidelines were followed (low cholesterol and animal fat) would have been sufficient to convince the readers. Figure 2 depicts mean LDL-C and adherence.

It was stated that adherence for oat bran was less compared to strawberries. Understandably, when participants were already eating oat bran in 1-year diet, their interest would be reduced for the elevated level. Figure 2 would have looked better had it been a bar diagram, indicating the parameters at given times, rather than as a change with time. There were 2-months intervals in 1-year study and only zero and 1-yr data is presented. Without intermittent data, the figure misleads as if adherence continued to increase within this 1-yr period. The most significant finding was that strawberry group exhibited reduced TBARS (absolute concentration and ratio with LDL-C) (Table 5).

If we look at corresponding LDL-C values in Table 3, it was reduced in oat bran group in 4-wk, but remained unchanged in strawberry group. In bran group also TBARS/ LDL-C values would have significantly lowered had the LDL-C concentration remained unchanged. Question as to why conjugated diene concentration did not reduce in strawberry group was not addressed. Both TBARS and conjugated diene concentrations represent extent of LDL oxidation.

In Table 5 protein thiols rose significantly in both 4-wk oat bran and strawberry groups, then how oat bran protected only protein oxidation and not the LDL? Figure 3 is just another representation of Table 5. If such artifacts are considered, an alternate interpretation might emerge, that is, strawberry ingredients only protect protein oxidation but may not affect LDL oxidation, or may be the tests are still insufficient to arrive to any firm conclusion.

Conclusion

The authors have provided evidence to support the hypothesis that strawberry ingredients reduce LDL oxidation in hyperlipidemic patients. In my opinion, if the aforementioned limitations were taken care of, perhaps the evidences would have been more conclusive. Unless the hypothesis is rigorously proven, the entire exercise of strawberry supplementation in diet for preventing atherogenesis and CHD risks would be defeated.

According to Fisher, Lees & Spence (2006, pp. 2431-2434), the same problems were encountered with vitamin C and E research. Consequently, elevated plasma homocysteine was attributed to oxidative stress-associated stroke and other cardiac conditions, preventable by folate and vitamins B₂ and B₁₂. It would be more appropriate to examine that, besides countering lipid peroxidation, whether strawberry has a role in reducing the serum homocysteine level, which has a direct implication in preventing CHD risks.

References

Aviram, M & Fuhrman, B 1998, ‘Polyphenolic flavonoids inhibit macrophage-mediated oxidation of LDL and attenuate atherogenesis’, Atherosclerosis, vol. 137 Suppl., pp. S45–S50.

Fisher, M, Lees, K & Spence, JD 2006,’ Nutrition and Stroke Prevention’, Stroke vol. 37, pp. 2430-2435.

Horgan, GW 2001,’ Statistical analysis of nutritional studies’, British Journal of Nutrition, vol. 86, pp. 141–144.

Jenkins, DJA, Kendall, CWC & Marchie, A 2005, ‘Diet and Cholesterol Reduction’, Annals of Internal Medicine, vol. 142.9, pp. 793-795.

Jenkins, DJA, Nguyen, TH, Kendall, CWC, Faulkner, DA, Bashyam, B, Kim, IJ, Ireland, C, Patel, D, Vidgen, E, Josse, AR, Sesso, HD, Burton-Freeman, B, Josse, RJ, Leiter, LA & Singer, W 2008, ‘The effect of strawberries in a cholesterol-lowering dietary portfolio’, Metabolism Clinical and Experimental, vol. 57, pp.1636–1644.

Seeram, NP 2007, ‘Strawberry Phytochemicals and Human Health: A Review’. Web.

Sniderman, AD, Blank, D, Zakarian, R, Bergeron, J & Frohlich, J 2003, ‘Triglycerides and small dense LDL: the twin Achilles heels of the Friedewald formula’, Clinical Biochemistry, vol. 36.7, pp. 499-504.

Walter, MF, Jacob, RF, Jeffers, Ghadanfar, MM, Preston, GM, Buch, J & Mason, RP 2004,’ Serum Levels of Thiobarbituric Acid Reactive Substances Predict Cardiovascular Events in Patients with Stable Coronary Artery Disease’, Journal of the American College of Cardiology, vol. 44.10, pp. 1996-2002.