In the present study, using dietary data from validated FFQs, we observed significant positive association between dietary animal-protein intake and plasma tHcy concentrations, and inverse relationship of plant-protein intake and plasma tHcy concentrations in coronary angiographic subjects. Furthermore, we found significant positive association between total-protein intake and plasma tCys concentrations. These associations between dietary protein and plasma tHcy or tCys concentrations appeared to be independent of age, sex, and other potential confounding factors.
The positive association between dietary intake of animal-protein and plasma tHcy has also been observed in a population-based study in Pakistani
. The association was strong and statistically significant in the population of the present study. This may be due to an increased intake of red meats, chicken, milk and dairy products, organ meats, and egg (rich sources of methionine)
. The only dietary precursor of homocysteine is the essential amino acid methionine
. Furthermore, in Chinese diets, meat and chicken are main sources of saturated fat. It has been shown that an increased dietary intake of saturated fat caused an increase in plasma tHcy concentrations
[10, 29]. Moreover, fish and fish oil supplements are rich sources of very-long-chain n-3 fatty acids. Dietary supplementation studies have reported conflicting results with respect to the effect of very-long-chain n-3 fatty acids on plasma tHcy concentrations. Some studies showed supplementation with fish or fish oil did not affect tHcy concentrations in hyperlipidemic subjects but increased tHcy concentrations in normlipidemic subjects
[30–32]. On the other hand, some studies reported fish oil could reduce the tHcy concentrations in hyperlipidemic and CVD patients
[33, 34]. Although we did not evaluate separately the association between the intake of fish and plasma tHcy concentrations, our present study considered the fish as sources of dietary animal-protein and showed a positive association between the dietary intake of animal-protein and plasma tHcy concentrations. Hence, the dietary intake of animal protein is an important determinant of plasma tHcy concentrations.
The inverse association between high plant-protein intake and plasma tHcy concentrations in present study is similar to the findings of some other studies
[22, 28]. It is well known that the high plant-protein diet patterns include cereals (rice and flour products including wheat and corn based flour), vegetables, fruit and fruit juices, legumes and soybean products, which are important food sources of folate and B vitamins. In the transmethylation pathway, homocysteine is remethylated to methionine in the presence of the enzyme methionine synthase. Folate and vitamin B12 are cofactors for methionine synthase, and therefore, are necessary for removal of homocysteine by transmethylation. Results from the Framingham Heart Study and the Health Professionals Follow-up Study all showed that frequent consumption of fruit and vegetables was associated with high plasma folate and low tHcy concentrations
[28, 35]. Furthermore, in the DASH study, after consuming a combination diet rich in fruit, vegetables and low fat diary products and reduced in saturated and total fat for 8 weeks, the plasma tHcy concentration was decreased and the change differed significantly from the control diet
. In the present study, we observed, as have others, that plasma tHcy concentration was inversely associated with plasma folate or vitamin B12 concentrations. Hence, the positive relationship of increased intake of the high plant-protein diet with plasma folate and vitamin B12 may partly explain why we found the low levels of plasma tHcy in individuals in the top quartile of high plant-protein dietary intake (Figure
1A), indicating that adequate consumption of fresh fruits and vegetables could be beneficial in reducing the risk of hyperhomocysteinemia. It has been shown that dietary intake is an important contributor to plasma vitamin B12. In the present study, we found plasma vitamin B12 was associated with plant protein intake but not with animal protein intake. This may be due to that plant protein coming from fermentation soybean products and organic plant products such as laver slice and mushrooms, which are frequently consumed by Chinese populations, contains enriched vitamin B12. Although vitamin B12 levels were lower in lowest quartile of the plant protein intake than that in lowest quartile of animal protein intake, this suggests that animal products are better sources of vitamin B12 than plant products, particularly milk and fish. Because vitamin B12 in meat is less bioavailable than that in milk and fish
, and we did not analyze the detailed associations between meat or milk and fish and vitamin B12, hence, combined different animal-source proteins may result in no significant association between vitamin B12 and animal protein intake.
Furthermore, we observed an adverse effect of high consumption of total protein on hypercysteinemia (Table
3). In multivariate regression analyses, we also found significant dose–response associations between total protein and animal protein intakes and plasma tCys concentrations. In addition, previous studies showed that plasma tCys was strongly related to several cardiovascular risk factors such as high cholesterol
[5, 11]. But few studies reported the effect of different dietary proteins on plasma tCys concentrations. In the present study, the high intake of total protein was positively associated with plasma tCys concentrations. This may be due to the high intake of total protein including high animal protein dietary products which are rich sources of methionine, the dietary precursor of homocysteine. Homocysteine is then degraded to cysteine by the sequential actions of two vitamin B6-dependent enzymes. In view of the strong association between tCys and total protein intake, it would be important to test whether tCys is associated with total plasma protein or plasma albumin, and is thus a marker of protein availability or nitrogen balance. Further studies are needed to demonstrate this hypothesis in the future.
An advantage of our study is that we conducted the study in a large population-based sample, using a validated FFQ. This allowed the investigation of the relationship of dietary protein intakes and tHcy and tCys concentrations. A few limitations should be considered when interpreting the findings of the present study. Collection of dietary data using a FFQ has inherent potential problems related to inaccuracy and potential misclassification in the estimation of protein intakes. The recall of past diets raises concerns regarding the possibility of recall bias among patients if their diets changed as a result of their diagnosis. It is also possible that the dietary intake interview reflected changes due to medical advice. To minimize the recall bias, patients were constantly reminded to report on their dietary intake before diagnosis with CAD. Furthermore, although we found plasma folate and vitamin B12 levels were significantly related to tHcy and adjusted for them in multivariate models, there are few patients with using B-vitamin supplements in our study population, this does not negate an effect of dietary vitamin supplements on plasma tHcy and tCys concentrations, which may mediate the relationship between dietary protein intake and tHcy and tCys concentrations. Finally, it was revealed that distinct dietary patterns were influenced by socio-economic and lifestyle characteristics. China has achieved remarkable economic progress in recent years. Accompanied with these rapid economic changes, dietary pattern is shifting from the traditional pattern with high intake of cereals and vegetables and low intake of animal foods to the Western pattern with high intake of animal foods and other high-energy-dense foods. Hence, there may be some differences or similarities of dietary protein levels and sources between Chinese and Western diets. For example, the levels of total dietary protein intake in Chinese populations may be lower than those in Western populations. The sources of dietary protein in Chinese diets are mainly from plant protein such as cereals, legumes and soybean products, whereas the sources of dietary protein in Western diets are mainly from animal protein such as red meats, chicken, milk and dairy products. These different sources of dietary protein between Chinese and Western diets may explain the differences of dietary protein levels. Consequently, it should be cautious to extrapolate our findings to other Western populations.